Ebook Fundamentals of biochemistry (5/E): Part 2

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(BQ) Part 2 book Fundamentals of biochemistry has contents: Glucose catabolism, glycogen metabolism and gluconeogenesis, citric acid cycle, electron transport and oxidative phosphorylation, nucleotide metabolism, nucleic acid structure, protein synthesis,... and other contents. CHAPTER 14 HAWOONG JEONG, UNIVERSITY OF NOTRE DAME / Science Source Images Introduction to Metabolism Chapter Contents Overview of Metabolism A Nutrition Involves Food Intake and Use B Vitamins and Minerals Assist Metabolic Reactions C Metabolic Pathways Consist of Series of Enzymatic Reactions D Thermodynamics Dictates the Direction and Regulatory Capacity of Metabolic Pathways E Metabolic Flux Must Be Controlled “High-Energy” Compounds A ATP Has a High Phosphoryl Group-Transfer Potential B Coupled Reactions Drive Endergonic Processes C Some Other Phosphorylated Compounds Have High Phosphoryl Group-Transfer Potentials D Thioesters Are Energy-Rich Compounds Oxidation–Reduction Reactions A NAD+ and FAD Are Electron Carriers B The Nernst Equation Describes Oxidation– Reduction Reactions C Spontaneity Can Be Determined by Measuring Reduction Potential Differences Experimental Approaches to the Study of Metabolism A Labeled Metabolites Can Be Traced B Studying Metabolic Pathways Often Involves Perturbing the System C Systems Biology Has Entered the Study of Metabolism Modern approaches to understanding metabolism include the use of network theory to probe the functional importance of interacting cellular components, such as the yeast proteins shown here Understanding the chemical compositions and three-dimensional structures of biological molecules is not sufficient to understand how they are assembled into organisms or how they function to sustain life We must therefore examine the reactions in which biological molecules are built and broken down We must also consider how free energy is consumed in building cellular materials and carrying out cellular work and how free energy is generated from organic or other sources Metabolism, the overall process through which living systems acquire and use free energy to carry out their various functions, is traditionally divided into two parts: Catabolism, or degradation, in which nutrients and cell constituents are broken down to salvage their components and/or to make energy available Anabolism, or biosynthesis, in which biomolecules are synthesized from simpler components In general, catabolic reactions carry out the exergonic oxidation of nutrient molecules The free energy thereby released is used to drive such endergonic processes as anabolic reactions, the performance of mechanical work, and the active transport of molecules against concentration gradients Exergonic and endergonic processes are often coupled through the intermediate synthesis of a “high-energy” compound such as ATP This simple principle underlies many of the chemical reactions presented in the following chapters In this chapter, we introduce the general features of metabolic reactions and the roles of ATP and other compounds as energy carriers Because many metabolic reactions are also oxidation–reduction reactions, we review the thermodynamics of these processes Finally, we examine some approaches to studying metabolic reactions 442 443 Overview of Metabolism KEY CONCEPTS • Different organisms use different strategies for capturing free energy from their environment and can be classified by their requirement for oxygen • Mammalian nutrition involves the intake of macronutrients (proteins, carbohydrates, and lipids) and micronutrients (vitamins and minerals) • A metabolic pathway is a series of enzyme-catalyzed reactions, often located in a specific part of a cell • The flux of material through a metabolic pathway varies with the activities of the enzymes that catalyze irreversible reactions • These flux-controlling enzymes are regulated by allosteric mechanisms, covalent modification, substrate cycling, and changes in gene expression A bewildering array of chemical reactions occur in any living cell Yet the principles that govern metabolism are the same in all organisms, a result of their common evolutionary origin and the constraints of the laws of thermodynamics In fact, many of the specific reactions of metabolism are common to all organisms, with variations due primarily to differences in the sources of the free energy that supports them A Nutrition Involves Food Intake and Use Nutrition, the intake and utilization of food, affects health, development, and performance Food supplies the energy that powers life processes and provides the raw materials to build and repair body tissues The nutritional requirements of an organism reflect its source of metabolic energy For example, some prokaryotes are autotrophs (Greek: autos, self + trophos, feeder), which can synthesize all their cellular constituents from simple molecules such as H2O, CO2, NH3, and H2S There are two possible free energy sources for this process Chemolithotrophs (Greek: lithos, stone) obtain their energy through the oxidation of inorganic compounds such as NH3, H2S, or even Fe2+: NH3 + O2 → HNO3 + H2O H2S + O2 → H2SO4 FeCO3 + O2 + H2O → Fe(OH) + CO2 Photoautotrophs so via photosynthesis, a process in which light energy powers the transfer of electrons from inorganic donors to CO2 to produce carbohydrates, (CH2O)n, which are later oxidized to release free energy Heterotrophs (Greek: hetero, other) obtain free energy through the oxidation of organic compounds (carbohydrates, lipids, and proteins) and hence ultimately depend on autotrophs for those substances Organisms can be further classified by the identity of the oxidizing agent for nutrient breakdown Obligate aerobes (which include animals) must use O2, whereas anaerobes employ oxidizing agents such as sulfate or nitrate Facultative anaerobes, such as E coli, can grow in either the presence or the absence of O2 Obligate anaerobes, in contrast, are poisoned by the presence of O2 Their metabolisms are thought to resemble those of the earliest life-forms, which arose more than 3.5 billion years ago when the earth’s atmosphere lacked O2 Most of our discussion of metabolism will focus on aerobic processes Animals are obligate aerobic heterotrophs, whose nutrition depends on a balanced intake of the macronutrients proteins, carbohydrates, and lipids These are broken down by the digestive system to their component amino acids, monosaccharides, fatty acids, and glycerol—the major nutrients involved in cellular metabolism—which are then transported by the circulatory system to the tissues The metabolic utilization of the latter substances also requires the intake of O2 and water, as well as micronutrients composed of vitamins and minerals Section Overview of Metabolism 444 TABLE 14-1 Characteristics of Common Vitamins Vitamin Coenzyme Product Reaction Mediated Human Deficiency Disease Water-Soluble Biotin (B7) Biocytin Carboxylation a Pantothenic acid (B5) Coenzyme A Acyl transfer a Cobalamin (B12) Cobalamin coenzymes Alkylation Pernicious anemia Riboflavin (B2) Flavin coenzymes Oxidation–reduction a — Lipoic acid Acyl transfer a Nicotinamide (niacin; B3) Nicotinamide coenzymes Oxidation–reduction Pellagra Pyridoxine (B6) Pyridoxal phosphate Amino group transfer a Folic acid (B9) Tetrahydrofolate One-carbon group transfer Megaloblastic anemia Thiamine (B1) Thiamine pyrophosphate Aldehyde transfer Beriberi Ascorbic acid (C) Ascorbate Hydroxylation Scurvy Vision Night blindness Fat-Soluble Vitamin A 2+ Vitamin D Ca Vitamin E Antioxidant a Vitamin K Blood clotting Hemorrhage absorption Rickets a No specific name; deficiency in humans is rare or unobserved TABLE 14-2 Major Essential Minerals and Trace Elements Major Minerals Trace Elements Sodium Iron Potassium Copper Chlorine Zinc Calcium Selenium Phosphorus Iodine Magnesium Chromium Sulfur Fluorine ? Which of the elements listed here occur as covalently bonded components of biological molecules? B Vitamins and Minerals Assist Metabolic Reactions Vitamins are organic molecules that an animal is unable to synthesize and must therefore obtain from its diet Vitamins can be divided into two groups: watersoluble vitamins and fat-soluble vitamins Table 14-1 lists many common vitamins and the types of reactions or processes in which they participate (we will consider the structures of these substances and their reaction mechanisms in the appropriate sections of the text) Table 14-2 lists the essential minerals and trace elements necessary for metabolism They participate in metabolic processes in many ways Mg2+, for example, is involved in nearly all reactions that involve ATP and other nucleotides, including the synthesis of DNA, RNA, and proteins Zn2+ is a cofactor in a variety of enzymes, including carbonic anhydrase (Section 11-3C) Ca2+, in addition to being the major mineral component of bones and teeth, is a vital participant in signal transduction processes (Section 13-4) Most Water-Soluble Vitamins Are Converted to Coenzymes Many coen- zymes (Section 11-1C) were discovered as growth factors for microorganisms or as substances that cure nutritional deficiency diseases in humans and/or animals For example, the NAD+ component nicotinamide, or its carboxylic acid analog nicotinic acid (niacin; Fig 14-1), relieves the ultimately fatal O O C C NH2 OH FIG 14-1 The structures of nicotinamide and nicotinic acid These vitamins form the redox-active components of the nicotinamide coenzymes NAD+ and NADP+ (compare with Fig 11-4) N Nicotinamide (niacinamide) N Nicotinic acid (niacin) 445 Section Overview of Metabolism dietary deficiency disease in humans known as pellagra Pellagra (Italian: pelle, skin + agra, sour), which is characterized by dermatitis, diarrhea, and dementia, was endemic in the rural southern United States in the early twentieth century Most animals, including humans, can synthesize nicotinamide from the amino acid tryptophan However, the corn (maize)-rich diet that was prevalent in the rural South contained little available nicotinamide or tryptophan from which to synthesize it (Corn actually contains significant quantities of niacin but in a form that requires treatment with base before it can be intestinally absorbed The Mexican Indians, who domesticated the corn plant but did not suffer from pellagra, customarily soak corn meal in lime water—dilute Ca(OH)2 solution—before using it to make their staple food, tortillas.) Dietary supplementation with nicotinamide or niacin has all but eliminated pellagra in the developed world The water-soluble vitamins in the human diet are all coenzyme precursors In contrast, the fat-soluble vitamins, with the exception of vitamin K (Section 9-1F), are not components of coenzymes, although they are also required in small amounts in the diets of many higher animals The distant ancestors of humans probably had the ability to synthesize the various vitamins, as many modern plants and microorganisms Yet since vitamins are normally available in the diets of animals, which all eat other organisms, or are synthesized by the bacteria that normally inhabit their digestive systems, it seems likely that the superfluous cellular machinery to synthesize them was lost through evolution For example, vitamin C (ascorbic acid) is required in the diets of only humans, apes, and guinea pigs (Section 6-1C and Box 6-2) because, in what is apparently a recent evolutionary loss, they lack a key enzyme for ascorbic acid biosynthesis C Metabolic Pathways Consist of Series of Enzymatic Reactions Metabolic pathways are series of connected enzymatic reactions that produce specific products Their reactants, intermediates, and products are referred to as metabolites There are around 4000 known metabolic reactions, each catalyzed by a distinct enzyme The types of enzymes and metabolites in a given cell vary with the identity of the organism, the cell type, its nutritional status, and its developmental stage Many metabolic pathways are branched and interconnected, so delineating a pathway from a network of thousands of reactions is somewhat arbitrary and is driven by tradition as much as by chemical logic In general, degradative and biosynthetic pathways are related as follows (Fig 14-2): In degradative pathways, the major nutrients, referred to as complex metabolites, are exergonically broken down into simpler products The free energy released in the degradative process is conserved by the synthesis of ATP Complex metabolites ADP + HPO2– NADP+ Degradation Biosynthesis NADPH Roles of ATP and NADP+ in metabolism ATP and NADPH, generated through the degradation of complex metabolites such as carbohydrates, lipids, and proteins, are sources of free energy for biosynthetic and other reactions FIG 14-2 ATP Simple products 446 Chapter 14 Introduction to Metabolism from ADP + Pi or by the reduction of a coenzyme such as NADP+ (Fig 11-4) to NADPH ATP and NADPH are the major free energy sources for biosynthetic reactions We will consider the thermodynamic properties of ATP and NADPH later in this chapter A striking characteristic of degradative metabolism is that the pathways for the catabolism of a large number of diverse substances (carbohydrates, lipids, and proteins) converge on a few common intermediates, in many cases, a two-carbon acetyl unit linked to coenzyme A to form acetyl-coenzyme A (acetyl-CoA; Section 14-2D) These intermediates are then further metabolized in a central oxidative pathway Figure 14-3 outlines the breakdown of various foodstuffs to their monomeric units and then to acetyl-CoA This is followed by the oxidation of the acetyl carbons to CO2 by the citric acid cycle (Chapter 17) When one substance is oxidized (loses electrons), another must be reduced (gain electrons; Box 14-1) The citric acid cycle thus produces the reduced coenzymes NADH and FADH2 (Section 14-3A), which then pass their electrons to O2 to produce H2O in the processes of electron transport and oxidative phosphorylation (Chapter 18) Biosynthetic pathways carry out the opposite process Relatively few metabolites serve as starting materials for a host of varied products In the next several chapters, we discuss many catabolic and anabolic pathways in detail Proteins Polysaccharides Triacylglycerols Amino acids Glucose Fatty acids + glycerol ADP ATP Glycolysis NAD+ NADH Pyruvate CO2 Acetyl-CoA Citric acid cycle NAD+ NADH FADH2 FAD NH3 CO2 NAD+ FAD Oxidative phosphorylation NADH FADH2 O2 ADP ATP H2O FIG 14-3 Overview of catabolism Complex metabolites such as carbohydrates, proteins, and lipids are degraded first to their monomeric units, chiefly glucose, amino acids, fatty acids, and glycerol, and then to the common intermediate, acetyl-CoA The acetyl group is oxidized to CO2 via the citric acid cycle with concomitant reduction of NAD+ and FAD to NADH and FADH2 Reoxidation of NADH and FADH2 by O2 during electron transport and oxidative phosphorylation yields H2O and ATP ? Identify the three major waste products of catabolism 447 Box 14-1 Perspectives in Biochemistry Oxidation States of Carbon The carbon atoms in biological molecules can assume different oxidation states depending on the atoms to which they are bonded For example, a carbon atom bonded to less electronegative hydrogen atoms is more reduced than a carbon atom bonded to highly electronegative oxygen atoms The simplest way to determine the oxidation number (and hence the oxidation state) of a particular carbon atom is to examine each of its bonds and assign the electrons to the more electronegative atom In a C—O bond, both electrons “belong” to O; in a C—H bond, both electrons “belong” to C; and in a C—C bond, each carbon “owns” one electron An atom’s oxidation number is the number of valence electrons on the free atom (4 for carbon) minus the number of its lone pair and assigned electrons For example, the oxidation number of carbon in CO2 is − (0 + 0) = +4, and the oxidation number of carbon in CH4 is − (0 + 8) = −4 Keep in mind, however, that oxidation numbers are only accounting devices; actual atomic charges are much closer to neutrality The following compounds are listed according to the oxidation state of the highlighted carbon atom In general, the more oxidized compounds have fewer electrons per C atom and are richer in oxygen, and the more reduced compounds have more electrons per C atom and are richer in hydrogen But note that not all reduction events (gain of electrons) or oxidation events (loss of electrons) are associated with bonding to oxygen For example, when an alkane is converted to an alkene, the formation of a carbon–carbon double bond involves the loss of electrons and therefore is an oxidation reaction although no oxygen is involved Knowing the oxidation number of a carbon atom is seldom required However, it is useful to be able to determine whether the oxidation state of a given atom increases or decreases during a chemical reaction Compound Formula Carbon dioxide O Acetic acid H3C C +4 (most oxidized) O O Carbon monoxide C C OH H C OH O Acetone H3C C CH3 O Acetaldehyde H3C C H O Acetylene +2 +1 H C HC +2 Formaldehyde H +3 +2 O O Formic acid Oxidation Number −1 CH H Ethanol H3C C OH −1 H H Ethene H2C C H −2 H Ethane H3C C H −3 H H Methane H C H Enzymes Catalyze the Reactions of Metabolic Pathways With a few exceptions, the interconversions of metabolites in degradative and biosynthetic pathways are catalyzed by enzymes In the absence of enzymes, the reactions would occur far too slowly to support life In addition, the specificity of enzymes guarantees the efficiency of metabolic reactions by preventing the formation of useless or toxic by-products Most importantly, enzymes provide a mechanism for coupling an endergonic chemical reaction (which would not occur on its own) with an energetically favorable reaction, as discussed below We will see examples of reactions catalyzed by all six classes of enzymes introduced in Section 11-1A These reactions fall into four major types: oxidations and reductions (catalyzed by oxidoreductases), group-transfer reactions (catalyzed by transferases and hydrolases), eliminations, isomerizations, and H −4 (least oxidized) 448 Chapter 14 Introduction to Metabolism rearrangements (catalyzed by isomerases and mutases), and reactions that make or break carbon–carbon bonds (catalyzed by hydrolases, lyases, and ligases) Metabolic Pathways Occur in Specific Cellular Locations The compartmentation of the eukaryotic cytoplasm allows different metabolic pathways to operate in different locations For example, electron transport and oxidative phosphorylation occur in the mitochondria, whereas glycolysis (a carbohydrate degradation pathway) and fatty acid biosynthesis occur in the cytosol Figure 14-4 shows the major metabolic functions of eukaryotic organelles Metabolic processes in prokaryotes, which lack organelles, may be localized to particular areas of the cytosol The synthesis of metabolites in specific membrane-bounded compartments in eukaryotic cells requires mechanisms to transport these substances between compartments Accordingly, transport proteins (Chapter 10) are essential components of many metabolic processes For example, a transport protein is required to move ATP, which is generated in the mitochondria, to the cytosol, where most of it is consumed (Section 18-1B) In multicellular organisms, compartmentation is carried a step further to the level of tissues and organs The mammalian liver, for example, is largely responsible for the synthesis of glucose from noncarbohydrate precursors (gluconeogenesis; Section 16-4) so as to maintain a relatively constant level of glucose in the circulation, whereas adipose tissue is specialized for storage of triacylglycerols The interdependence of the metabolic functions of the various organs is the subject of Chapter 22 Cytosol Glycolysis, pentose phosphate pathway, fatty acid biosynthesis, many reactions of gluconeogenesis Rough endoplasmic reticulum Synthesis of membrane-bound and secretory proteins Smooth endoplasmic reticulum Lipid and steroid biosynthesis Nucleus DNA replication and transcription, RNA processing Mitochondrion Citric acid cycle, electron transport and oxidative phosphorylation, fatty acid oxidation, amino acid breakdown Peroxisome (glyoxysome in plants) Oxidative reactions catalyzed by amino acid oxidases and catalase; glyoxylate cycle reactions in plants Golgi apparatus Posttranslational processing of membrane & secretory proteins; formation of plasma membrane and secretory vesicles Lysosome Enzymatic digestion of cell components and ingested matter FIG 14-4 Metabolic functions of eukaryotic organelles Degradative and biosynthetic processes may occur in specialized compartments in the cell, or may involve several compartments ? Without looking at the figure, summarize the major function of each cellular compartment Identify which compartments carry out degradative versus synthetic processes 449 An intriguing manifestation of specialization of tissues and subcellular compartments is the existence of isozymes, enzymes that catalyze the same reaction but are encoded by different genes and have different kinetic or regulatory properties For example, we have seen that mammals have three isozymes of glycogen phosphorylase, those expressed in muscle, brain, and liver (Section 12-3B) Similarly, vertebrates possess two homologs of the enzyme lactate dehydrogenase: the M type, which predominates in tissues subject to anaerobic conditions such as skeletal muscle and liver, and the H type, which predominates in aerobic tissues such as heart muscle Lactate dehydrogenase catalyzes the interconversion of pyruvate, a product of glycolysis, and lactate (Section 15-3A) The M-type isozyme appears mainly to function in the reduction by NADH of pyruvate to lactate, whereas the H-type enzyme appears to be better adapted to catalyze the reverse reaction The existence of isozymes allows for the testing of various illnesses For example, heart attacks cause the death of heart muscle cells, which consequently rupture and release H-type LDH into the blood A blood test indicating the presence of H-type LDH is therefore diagnostic of a heart attack Section Overview of Metabolism D Thermodynamics Dictates the Direction and Regulatory Capacity of Metabolic Pathways Knowing the location of a metabolic pathway and enumerating its substrates and products does not necessarily reveal how that pathway functions as part of a larger network of interrelated biochemical processes It is also necessary to appreciate how fast end product can be generated by the pathway, as well as how pathway activity is regulated as the cell’s needs change Conclusions about a pathway’s output and its potential for regulation can be gleaned from information about the thermodynamics of each enzyme-catalyzed step Recall from Section 1-3D that the free energy change ΔG of a biochemical process, such as the reaction A+B⇌ C+D is related to the standard free energy change (ΔG°′) and the concentrations of the reactants and products (Eq 1-15): ΔG = ΔG°′ + RT ln ( [C] [ D] [A] [ B] ) [14-1] At equilibrium, ΔG = and the equation becomes ΔG°′ = −RT ln Keq [14-2] Thus, the value of ΔG°′ can be calculated from the equilibrium constant and vice versa (see Sample Calculation 14-1) When the reactants are present at values close to their equilibrium values, [C]eq[D]eq/[A]eq[B]eq ≈ Keq, and ΔG ≈ This is the case for many metabolic reactions, which are said to be near-equilibrium reactions Because their ΔG values are close to zero, they can be relatively easily reversed by changing the ratio of products to reactants When the reactants are in excess of their equilibrium concentrations, the net reaction proceeds in the forward direction until the excess reactants have been converted to products and equilibrium is attained Conversely, when products are in excess, the net reaction proceeds in the reverse direction to convert products to reactants until the equilibrium concentration ratio is again achieved Enzymes that catalyze near-equilibrium reactions tend to act quickly to restore equilibrium concentrations, and the net rates of such reactions are effectively controlled by the relative concentrations of substrates and products SAMPLE CALCULATION 14-1 Calculate the equilibrium constant for the hydrolysis of glucose-1-phosphate at 37°C, using the information in Table 14-3 (see Section 14-2A) ΔG°′ for the reaction Glucose-1-phosphate + H2O → glucose + Pi is −20.9 kJ · mol−1 At equilibrium, ΔG = and Eq 14-1 becomes ΔG°′ = −RT ln K (Eq 14-2) Therefore, K = e−ΔG°′/RT −1 −1 −1 K = e−(−20,900 J·mol )/(8.3145 J·K ·mol )(310 K) K = 3.3 × 103 See Sample Calculation Videos GATEWAY CONCEPT Le Châtelier’s Principle Recall from Chapter that adding or removing components from a reaction at equilibrium causes the reaction to proceed in one direction or the other until a new equilibrium is established 450 GATEWAY CONCEPT Free Energy Change You can think of the free energy change (ΔG) for a reaction in terms of an urge or a force pushing the reactants toward equilibrium The larger the free energy change, the farther the reaction is from equilibrium and the stronger is the tendency for the reaction to proceed At equilibrium, of course, the reactants undergo no net change and ΔG = Other metabolic reactions function far from equilibrium; that is, they are irreversible This is because an enzyme catalyzing such a reaction has insufficient catalytic activity (the rate of the reaction it catalyzes is too slow) to allow the reaction to come to equilibrium under physiological conditions Reactants therefore accumulate in large excess of their equilibrium amounts, making ΔG ≪ Changes in substrate concentrations therefore have relatively little effect on the rate of an irreversible reaction; the enzyme is essentially saturated Only changes in the activity of the enzyme—through allosteric interactions, for example—can significantly alter the rate The enzyme is therefore analogous to a dam on a river: It controls the flow of substrate through the reaction by varying its activity, much as a dam controls the flow of a river by varying the opening of its floodgates Understanding the flux (rate of flow) of metabolites through a metabolic pathway requires knowledge of which reactions are functioning near equilibrium and which are far from it Most enzymes in a metabolic pathway operate near equilibrium and therefore have net rates that vary with their substrate concentrations However, certain enzymes that operate far from equilibrium are strategically located in metabolic pathways This has several important implications: Metabolic pathways are irreversible A highly exergonic reaction (one with ΔG ≪ 0) is irreversible; that is, it goes to completion If such a reaction is part of a multistep pathway, it confers directionality on the pathway; that is, it makes the entire pathway irreversible Every metabolic pathway has a first committed step Although most reactions in a metabolic pathway function close to equilibrium, there is generally an irreversible (exergonic) reaction early in the pathway that “commits” its product to continue down the pathway (likewise, water that has gone over a dam cannot spontaneously return) Catabolic and anabolic pathways differ If a metabolite is converted to another metabolite by an exergonic process, free energy must be supplied to convert the second metabolite back to the first This energetically “uphill” process requires a different pathway for at least one of the reaction steps A Y X The existence of independent interconversion routes, as we will see, is an important property of metabolic pathways because it allows independent control of the two processes If metabolite is required by the cell, it is necessary to “turn off” the pathway from to while “turning on” the pathway from to Such independent control would be impossible without different pathways E Metabolic Flux Must Be Controlled GATEWAY CONCEPT The Steady State Although many reactions are near equilibrium, an entire metabolic pathway—and the cell’s metabolism as a whole—never reaches equilibrium This is because materials and energy are constantly entering and leaving the system, which is in a steady state Metabolic pathways proceed, as if trying to reach equilibrium (Le Châtelier’s principle), but they cannot get there because new reactants keep arriving and products not accumulate Living organisms are thermodynamically open systems that tend to maintain a steady state rather than reaching equilibrium (Section 1-3E) This is strikingly demonstrated by the observation that, over a 40-year time span, a normal human adult consumes literally tons of nutrients and imbibes more than 20,000 L of water but does so without major weight change The flux of intermediates through a metabolic pathway in a steady state is more or less constant; that is, the rates of synthesis and breakdown of each pathway intermediate maintain it at a constant concentration A steady state far from equilibrium is thermodynamically efficient, because only a nonequilibrium process (ΔG ≠ 0) can perform useful work Indeed, living systems that have reached equilibrium are dead Since a metabolic pathway is a series of enzyme-catalyzed reactions, it is easiest to describe the flux of metabolites through the pathway by considering its 451 reaction steps individually The flux of metabolites, J, through each reaction step is the rate of the forward reaction, vf , less that of the reverse reaction, vr : J = vf − vr [14-3] At equilibrium, by definition, there is no flux (J = 0), although vf and vr may be quite large In reactions that are far from equilibrium, vf ≫ vr , the flux is essentially equal to the rate of the forward reaction (J ≈ vf) For the pathway as a whole, flux is set by the rate-determining step of the pathway By definition, this step is the pathway’s slowest step, which is often the first committed step of the pathway In some pathways, flux control is distributed over several enzymes, all of which help determine the overall rate of flow of metabolites through the pathway Because a rate-determining step is slow relative to other steps in the pathway, its product is removed by succeeding steps in the pathway before it can equilibrate with reactant Thus, the rate-determining step functions far from equilibrium and has a large negative free energy change In an analogous manner, a dam creates a difference in water levels between its upstream and downstream sides, and a large negative free energy change results from the hydrostatic pressure difference The dam can release water to generate electricity, varying the water flow according to the need for electrical power Reactions that function near equilibrium respond rapidly to changes in substrate concentration For example, upon a sudden increase in the concentration of a reactant for a near-equilibrium reaction, the enzyme catalyzing it would increase the net reaction rate to rapidly achieve the new equilibrium level Thus, a series of near-equilibrium reactions downstream from the rate-determining step all have the same flux Likewise, the flux of water in a river is the same at all points downstream from a dam In practice, it is often possible to identify flux control points for a pathway by identifying reactions that have large negative free energy changes The relative insensitivity of the rates of these nonequilibrium reactions to variations in the concentrations of their substrates permits the establishment of a steady state flux of metabolites through the pathway Of course, flux through a pathway must vary in response to the organism’s requirements to reach a new steady state Altering the rates of the rate-determining steps can alter the flux of material through the entire pathway, often by an order of magnitude or more Cells use several mechanisms to control flux through the rate-determining steps of metabolic pathways: Allosteric control Many enzymes are allosterically regulated (Section 12-3A) by effectors that are often substrates, products, or coenzymes of the pathway but not necessarily of the enzyme in question For example, in negative feedback regulation, the product of a pathway inhibits an earlier step in the pathway: A B C P Thus, as we have seen, CTP, a product of pyrimidine biosynthesis, inhibits ATCase, which catalyzes the rate-determining step in the pathway (Fig 12-11) Covalent modification Many enzymes that control pathway fluxes have specific sites that may be enzymatically phosphorylated and dephosphorylated (Section 12-3B) or covalently modified in some other way Such enzymatic modification processes, which are themselves subject to control by external signals such as hormones (Section 13-1), greatly alter the activities of the modified enzymes The signaling methods involved in such flux control mechanisms are discussed in Chapter 13 Section Overview of Metabolism Index Nomenclature: amino acid, 87–88, 88F enzyme, 324 Noncoding RNAs (ncRNAs), 938, 939T, 1037 Noncoding (antisense) strand, 941, 941F Noncooperative binding, 188 Noncovalent interactions, 49, 158–159 Non-equilibrium steady state, 19–20 Nonessential amino acids, 747–752, 747T Nonheme iron proteins, 598 Nonhomologous end-joining (NHEJ), 914–915 Non-insulin-dependent diabetes mellitus, 793–795 Nonketotic hyperglycinemia, 735 Nonmediated membrane transport, 294–295, 308 Nonpolar molecules, 27–29, 29F, 104 Nonpolar side chains, amino acid, 82T, 84, 85F, 149 Nonpolar solutes, 28, 28F Nonreceptor tyrosine kinases (NRTKs), 417–420, 1066 Nonreducing sugars, 227 Nonsense codons, 986 Nonsense-mediated decay (NMD), 1070 Nonsense mutations, 1024 Nonsense suppressors, 1024 Nonshivering thermogenesis, 507, 620 Nonsteroidal anti-inflammatory drugs (NSAIDs), 705 Non-stop decay, 1070 Non Watson–Crick base pairs, 849, 849F N-nonyl-β-D-glucopyranoside, 308F Norepinephrine (noradrenaline): and fatty acid metabolism, 698 and fuel metabolism, 783 function, 405–406 and glycogen metabolism, 542, 543 synthesis of, from amino acids, 762, 763F and thermogenesis, 790 Northern blot, 859 Notophthalmus viridescens, 1038F Novobiocin, 848 NPCs (nuclear pore complexes), 972 NRTKs (nonreceptor tyrosine kinases), 417–420, 1066 NSAIDs (nonsteroidal anti-inflammatory drugs), 705 N-terminal “headpiece,” lac repressor, 1045 N-terminus (amino terminus): end-group analysis, 110, 112 peptide bonds at, 84 as starting end of polypeptide synthesis, 1004, 1004F NTP (nucleoside triphosphate), 459–460, 807 Nuclear magnetic resonance (NMR): determining protein structure with, 147–149, 148F metabolic pathway studies, 470, 470F 2D, 148 Nuclear Overhauser spectroscopy (NOESY), 148, 148F Nuclear pore complexes (NPCs), 972 Nuclear receptors, 1068–1069, 1069F Nuclear receptor superfamily, 1068 Nuclear territories, chromosome, 874, 874F Nucleases, 101, 856, 1072–1074 See also specific nucleases Nucleic acids, 42 charges of, 850 chromatography, 856 electrophoresis, 857–859, 857F fractionation, 856–859 function, 50–53 genetic information in, 831–832 ionic interactions, 850 single-stranded, 50 stabilizing forces, 848–856 stacking interactions, 849, 850, 850F, 850T structure, 46–50, 46F Nucleic Acid Database (NDB), 156–157 Nucleic acid sequencing, 53–66 chain-terminator method, 57–59, 58F databases, 118–119, 118T electrophoresis, 56–57 gel electrophoresis, 56F, 59, 59F of genomes, 62–63 mutations and evolution, 63–66 ordering DNA fragments, 59, 59F restriction endonucleases, 54–56 sequencing-by-synthesis methods, 59–61 Nucleic acid structure, 831–875 DNA helix, 832–848 DNA–protein interactions, 859–867 eukaryotic chromosome structure, 868–874 fractionation of nucleic acids, 856–859 stabilizing forces, 848–856 Nucleolus, 973 Nucleophilic catalysis, 334–335 Nucleophilic groups, 335F Nucleoporins, 972 Nucleosidases, 820 Nucleosides, 43, 44T Nucleoside diphosphate (NDP), 459, 807, 813, 816F Nucleoside diphosphate kinases, 459, 807 Nucleoside monophosphates, 807 Nucleoside monophosphate kinases, 807 Nucleoside phosphorylases, 820 Nucleoside triphosphate (NTP), 459–460, 807 Nucleosomes: and chromosome structure, 868–870 DNA in eukaryotes, 1053–1054, 1054F, 1055F histone binding to, 871F histone modifications on, 1056F and replication forks, 902 Nucleosome core particle, 869, 869F, 870F Nucleotides, 43–45, 44T biosynthesis, 757 chemical structures, 43, 43F databases of, 61 defined, 42 determining sequence of, see Nucleic acid sequencing DNA polymerase and correctly paired, 883–888 in metabolic reactions, 44–45 in nucleic acids, 46–47 and site-directed mutagenesis, 73–74 and sugar-phosphate backbone, 839F torsion angles and conformation, 838F Nucleotide bases, 44T, 47 and Chargaff’s rules, 47 and methyltransferases, 1060–1062 point mutations and altered, 906–907 tautomeric forms of, 47F termination of DNA synthesis, 58–59 of tRNAs, 989 Nucleotide degradation, 820–827 purine catabolism, 822–825 pyrimidine breakdown, 827 uric acid degradation, 825–826 Nucleotide excision repair (NER), 912–913, 912F Nucleotide metabolism, 802–828, 822F deoxyribonucleotide formation, 812–820 nucleotide degradation, 820–827 purine ribonucleotide synthesis, 802–809 pyrimidine ribonucleotide synthesis, 809–812 Nucleotide residues, 46 Nucleotide sugars, 552, 552F Nucleotidyl transfer, 887, 887F Nucleus, 7, 448F, 972–973 Nurse cells, 1089 Nüsslein-Volhard, Christiane, 1090, 1091 Nutrasweet®, 229, 746 Nutrition, 443 nvCJD (new variant CJD), 174 Nyborg, Jens, 1012 Obesity, 507, 789, 794–796 Obligate aerobes, 443 Obligate anaerobes, 443 Ocean acidification, 34 Ochoa, Severo, 526, 985 Octahedral symmetry, 159F Octanoyl-CoA, 675 ODCase (OMP decarboxylase), 810 Odd-chain fatty acid oxidation, 678–684 Knoop experiment, 672F methylmalonyl-CoA mutase, 680, 682 succinyl-CoA, 682–684 O’Donnell, Michael, 893 OEC (oxygen-evolving center), 642–644, 644F Ogston, Alexander, 571 Oils, 248 Okazaki, Reiji, 881 Okazaki fragments: and activity of DNA polymerases, 884, 884F I-23 in semidiscontinuous replication, 881, 882 and sliding clamp mechanism, 893, 894 Oleate, 29F Oleic acid, 246, 246F, 676 Oligomers, 47, 158, 159F Oligonucleotides, 54F Oligopeptides, 84 Oligosaccharides, 228 dynamics of, 240F and glycoproteins, 240–242 in glycosylation, 1029, 1029F high-mannose, 239 N-linked, 235, 238–239, 553–555 O-linked, 235, 240, 553, 553F processing of, 238–239 in proteoglycans, 235F O-linked oligosaccharides, 235, 240, 553, 553F OMIM (Online Mendelian Inheritance in Man) database, 1037 OMP (orotidine-5′-monophosphate), in UMP synthesis, 809F, 810 OMP decarboxylase (ODCase), in UMP synthesis, 810 OmpF porin, 266F, 297 Oncogenes, 416 One gene–one enzyme theory, 51, 52 Online Mendelian Inheritance in Man (OMIM) database, 1037 Oparin, Alexander, Open complex, 940 Open reading frame (ORF), 63, 1035, 1036 Open systems, 18–19 Operators, 861, 1044–1045, 1045F Operons, 941 his, 1050 ilv, 1050 lac, 941, 941F, 1043–1046, 1044F trp, 941, 1048–1050, 1048F, 1050F Optical activity, 88, 89 Optical density, 101 Oral rehydration therapy, 316 ORC (origin recognition complex), 901 Ordered mechanisms, 372–373 ORF, see Open reading frame Organelles, 8, 8F, 448F Organic arsenicals, 568 Organic compounds, Organic synthesis, chiral, 90 Organisms: continuous evolution of, 10–11 diploid, 49 evolutionary domains of, 9–10, 9F transformation of, 51, 51F transgenic, 74–75, 74F Organ specialization, 774–781 adipose tissue, 778 blood, 780–781 brain, 775–776 kidney, 780 liver, 778–780 muscle, 776–778 oriC locus, 889 Orientation effects (enzymes), 336–338, 337F Origin-independent replication restart, 924 Origin recognition complex (ORC), 901 Ornithine: in amino acid degradation, 737F biosynthesis, 751, 751F, 752 in urea cycle, 730F, 731–732 Ornithine-δ-aminotransferase, 752 Ornithine transcarbamoylase, 731–732 Orotate, 809F, 810 Orotate phosphoribosyl transferase, 810 Orotic aciduria, 812 Orotidine-5′-monophosphate (OMP), 809F, 810 Orphan genes, 1036 Orthologous proteins, 124 Orthophosphate cleavage, 457 Oseltamivir (Tamiflu), 375, 375F Oseltamivir carboxylate, 375 Osmosis, 29–31 Osmotic pressure, 30, 30F Osteogenesis imperfecta (brittle bone disease), 143 Ouabain, 312 Ovalbumin, 963F, 964 Overproducers, 72 I-24 Index Oxalate, 309 Oxaloacetate: in amino acid biosynthesis, 581, 748–749, 748F in amino acid degradation, 725, 733F, 736–737 from cancer metabolism, 798 in citric acid cycle, 559, 560F, 568–570, 574–575, 578 in gluconeogenesis, 544–548, 545F–547F in glyoxylate cycle, 584F in tricarboxylate transport system, 688F in urea cycle, 730F Oxalosuccinate, 571, 571F Oxidant, 463 Oxidation, 447 See also Fatty acid oxidation acyl-CoA, 742–743 photo-, 636, 638–639 Oxidation–reduction reactions, 463–467 cytochrome c in, 608–609 in electron transport, 596 FAD in, 462–463 NAD+ in, 462–463 Nernst equation for, 463–465 in pentose phosphate pathway, 514–515 redox centers, 588 reduction potential measurements, 465–467 Oxidative deamination, 728, 906, 906F Oxidative metabolism, 558, 559F aerobic, 623–626 control of, 620–626 coordinated control of, 623 rate of oxidative phosphorylation, 622–623 Oxidative phosphorylation, 609–620 ATP synthase in, 610, 613–618 in catabolism, 446 chemiosmotic theory, 610–613 control, 622–623 high-energy compounds in, 458 in mammalian metabolism, 775 and mitochondrial electron transport, 589 NAD+ from, 496 P/O ratio, 618–619 uncoupling, 619–620 Oxidized (term), 446 Oxidizing agents, 463 2,3-Oxidosqualene, 710, 711F Oxidosqualene cyclase, 710, 711F 2-Oxoglutarate, 571 8-Oxoguanine (oxoG), 906 Oxonium ion, 342, 344 6-Oxo-PGF1α, 258F Oxyanion hole, 350, 355 Oxygen: affinities, 190–197 diffusion, 183 inactivation of nitrogenase by, 768 in photosynthesis, 630, 631, 639–650 reactive species, 602, 624, 625 reduction of, 607–609, 618–619, 624, 625 from water-splitting reaction, 643–644, 643F, 644F Oxygenation, 182 Oxygen binding, 181–200 and affinities for oxygen, 190–197 cooperative, 187–190 by hemoglobin, 185–200 and mutations in hemoglobin, 197–200 by myoglobin, 181–184, 184F Oxygen binding curves, 183–184, 184F, 188–190 Oxygen debt, 781 Oxygen deprivation, 625 Oxygen-evolving center (OEC), 642–644, 644F Oxygen transport, 192–194, 193F Oxygen-transport proteins, 185 Oxyhemoglobin, 186, 187F P (proofreading site), RNAP, 954 p14ARF protein, 1084 p21Cip1 gene, 1083 p50, 184 p51, 900, 901 p53 gene, 1082–1085 p53 protein, 1082–1085, 1084F p66, 900, 901 P680, 643, 649 P700, 646, 647, 649 P870, 637 P960, 637 PAB II (Poly(A) binding protein II), 962 Pabo, Carl, 864, 1094 PABP (Poly(A) binding protein), 963 PAF65α, 1057 PAF65β, 1057 PAGE, see Polyacrylamide gel electrophoresis PAgK84, restriction digests, 56F Pair-rule genes, 1090–1092 PALA (N-(phosphonacetyl)-L-aspartate), 385 Palindromic DNA sequences, 55 Palmitate, 29F, 691F, 695 Palmitic acid, 246 1-Palmitoleoyl-2-linoleoyl-3-stearoylglycerol, 248 1-Palmitoyl-2,3-dioleoyl-glycerol, 665 Palmitoyl-ACP, 691F, 692 Palmitoylation, 268 Palmitoyl-CoA, 703–704, 704F Palmitoyl thioesterase (TE), 268, 692 Pancreatic β cells, 793 Pancreatic DNase I, 841 Pancreatic islets, 404–405 Pancreatic lipase, 666, 666F Pantothenic acid (vitamin B3), 461 PAP (Poly(A) polymerase), 962 Papain, 213 Parallel β sheet, 138, 138F Paralogous genes, 124 Paraoxonase, 346 Parathion, 346 Parkinson’s disease, 175, 624, 762 Parnas, Jacob, 479 Paromomycin, 1031 – Partial molar free energy (GA), 16, 294 Partial oxygen pressure (pO2), 184, 189–190 Passenger RNA, 1073 Passive-mediated transport, 295–309 aquaporins, 304–305 ion channels, 297–304 ionophores, 295–297 porins, 297 transport proteins, 305–309 Pasteur, Louis, 322, 323, 478 Pasteur effect, 502 Patel, Dinshaw, 1051 Pathogens, 212 Pauling, Linus, 132, 135–136, 138, 198, 203, 338, 366, 833 Pavletich, Nikola, 1083 PBG (porphobilinogen), 758, 759F P body (processing body), 1070 PbRCs, see Purple photosynthetic bacteria reaction centers pbx (postbithorax) mutant, 1091 PC, see Plastocyanin PCAF complex, 1057 P-cluster, nitrogenase, 765 PCNA, see Proliferating cell nuclear antigen PCR (polymerase chain reaction), 71–72, 72F PDB (Protein Data Bank), 155–157 PDBid, 156 PDI (protein disulfide isomerase), 168, 169F PDK1 (phosphoinositide-dependent protein kinase-1), 439 PE, see Phosphatidylethanolamine Pebay-Peyrola, Eva, 592 Pectins, 234 Pellagra, 445 Penicillin, 238, 680 Penicillinase, 238 Penicillium notatum, 238 Pentose, 223 Pentose phosphate pathway, 479, 512–519, 513F carbon-carbon bond cleavage and formation, 515–517 and glycolysis, 518, 519F NADPH production, 514–515 regulation of, 518, 519 ribulose-5-phosphate isomerization and epimerization, 515 PEP, see Phosphoenolpyruvate PEPCK, see Phosphoenolpyruvate carboxykinase (PEP carboxykinase) Pepsin, 131, 376, 680, 724 Peptidases, 90, 91 Peptides, 98 See also Polypeptides as chymotrypsin substrates, 325–326 fusion, 287, 288 mass spectrometry sequencing of, 117–118 and polypeptide conformation, 132–135 signal, 277, 278 Peptide-N4-(N-acetyl-β-D-glucosaminyl)asparagine amidase F, 153F Peptide bonds, 84, 372, 1016, 1017 Peptide groups, 133 planar, 132–135 steric interference of, 134F torsion angles between, 133, 134 trans, 133F Peptidoglycans, 235–238, 237F Peptidomimetic drugs, 377 Peptidyl homoserine lactone, 114F Peptidyl site (P), 1001, 1002 Peptidyl transfer, 1016–1017, 1017F Peptidyl transferase, 1004, 1005, 1005F Peptidyl-tRNA, 1001, 1005, 1015 Peptidyl-tRNA hydrolase, 1031 Peptococcus aerogenes, 648F Perioxisome proliferator–activated receptor-γ (PPAR-γ), 795 Peripheral membrane proteins, 268 Peripheral tissues, chylomicrons in, 668, 669 Permeases, 295 See also Lactose permease (galactoside permease) Pernicious anemia, 680 Peroxidase, 704 Peroxisomal β oxidation, 684 Peroxisomes, 8, 448F, 684, 684F Peroxynitrite, 764 Pertussis, 431 Pertussis toxin, 431 Perutz, Max, 185, 186, 190, 203, 833 Perutz mechanism, 190–192, 190F, 191F PEST proteins, 721 Pfam (computer program), 157 PFGE (pulsed-field gel electrophoresis), 857, 857F PFK, see Phosphofructokinase PFK-2 (phosphofructokinase-2), 549–551, 550F PFK-2/FBPase-2 complex, 786–787 2PG, see 2-Phosphoglycerate 3PG, see 3-Phosphoglycerate PGFα, 258F PGH2, 705 PGH2 (prostaglandin H2), 258F PGI (phosphoglucose isomerase), 482–484, 483F PGK (phosphoglycerate kinase), 491–492, 491F P-glycoprotein, 314, 314F, 315F PGM, see Phosphoglycerate mutase pH, 33–39 acid and base impact on, 33–36 biochemical standard state, 17 of blood, 780 and buffers, 36–39 of common substances, 33T defined, 32 enzyme effects, 332 and ion concentrations, 33F and protein denaturation, 162 and protein stability, 100 Phage λ, see Bacteriophage λ Phagocytosis, 211F Pharmacogenomics, 397 Pharmacokinetics, 393 Pharming, 75 Phase I clinical trials, 394 Phase II clinical trials, 394 Phase III clinical trials, 394 Phase transition, in lipid bilayer, 261F PHD finger, 1060 Phe, see Phenylalanine Phen (phentermine), 394 Phenotypes, 64, 472F Phenotypically silent codons, 986 Phentermine (phen), 394 Phentolamine, 405 Phenylacetic acid, 672 Phenylaceturic acid, 672 Phenylalanine (Phe): biosynthesis, 755, 755F breakdown, 471F, 745, 745F, 746, 747F genetic code specification, 985 Index nonpolar side chain, 84, 85F UV absorbance spectra, 102F Phenylalanine hydroxylase, 745, 747F 2-Phenylethanol, 771 Phenylisothiocyanate (PITC), 114, 115F Phenylketonuria (PKU), 229, 746 Phenylpyruvate, 746 Phenylthiocarbamyl (PTC), 114, 115F Phenylthiohydantoin (PTH), 115F, 116 Pheophytin a (Pheo a), 642 Phe–tRNAPhe, 1012F ϕ angle, 133, 134 Philadelphia chromosome, 420 Phillips, David, 340, 341 Phillips, Simon, 862 Phorbol-13-acetate, 437, 437F Phosphagens, 459 Phosphatases, 402 Phosphate, 36F, 593 Phosphate carrier, 593 Phosphatidic acid, 249, 696F, 703F Phosphatidic acid phosphatase, 696 Phosphatidylcholine (lecithin), 701, 701F Phosphatidylethanolamine (PE), 274, 275F, 701, 701F, 702 Phosphatidylethanolamine serine transferase, 701, 702 Phosphatidylglycerol, 702, 703F Phosphatidylglycerol phosphate, 702, 703F Phosphatidylinositol, 258, 702, 703F Phosphatidylinositol-4,5-bisphosphate (PIP2), 434, 434F Phosphatidylserine, 701, 702 Phosphoanhydrides, 455F, 456–457 Phosphoanhydride bond, 454 Phosphoarginine, 458, 459 Phosphocholine, 701F Phosphocreatine, 458, 459, 777 Phosphodiesterases, 432 Phosphodiester bond, 46 Phosphoenolpyruvate (PEP): in amino acid biosynthesis, 755F formation, 547F and free energy of phosphate hydrolysis, 456, 456F in gluconeogenesis, 545–549, 545F, 546F in glycolysis, 493–495 hydrolysis, 495F metabolite transport, 548–549, 548F Phosphoenolpyruvate carboxykinase (PEPCK; PEP carboxykinase), 546–548, 548F, 697 Phosphoester bond, 454 Phosphoethanolamine, 701F Phosphofructokinase (PFK): citrate inhibition, 623 deactivation by thioredoxin, 658 and F6P concentration, 504, 504F, 505 in glycolysis, 484, 503–506 substrate cycling and regulation of, 507F X-ray structure, 504F Phosphofructokinase-2 (PFK-2), 549–551, 550F Phosphofructokinase-2/fructose bisphosphatase-2, 797 Phosphoglucomutase: Carl and Gerty Coris’ study of, 526 in galactose conversion, 510 in glycogen breakdown, 525, 529–531 mechanism of, 529F 6-Phosphogluconate, 513F, 514, 515F 6-Phosphogluconate dehydrogenase, 514, 515 6-Phosphogluconolactonase, 514 6-Phosphoglucono-δ-lactone, 513F, 514 Phosphoglucose isomerase (PGI), 482–484, 483F 2-Phosphoglycerate (2PG), 21, 492–494, 545F 3-Phosphoglycerate (3PG), 21 amino acid biosynthesis from, 752, 752F ATP and PGK in complex with, 491F and 2,3-BPG, 494 in Calvin cycle, 651, 653F in gluconeogenesis, 545F in glycolysis, 491–493 in photorespiration, 659F Phosphoglycerate kinase (PGK), 491–492, 491F Phosphoglycerate mutase (PGM), 492–493, 492F, 493F Phosphoglycerides, see Glycerophospholipids 3-Phosphoglycerol, 591F, 592 3-Phosphoglycerol dehydrogenase, 592 Phosphoglycohydroxamate, 487 2-Phosphoglycolate, 487, 487F, 658, 659F Phosphoglycolate phosphatase, 658 Phosphoguanidines, 458–459 3-Phosphohydroxypyruvate, 752, 752F Phosphoinositide-dependent protein kinase-1 (PDK1), 439 Phosphoinositide 3-kinases (PI3Ks), 438–439 Phosphoinositide pathway, 432–439, 433F and calmodulin, 434–436 and diacylglycerol, 436–437 and emergent properties of complex systems, 437–439 and ligand binding, 433–434 other signal transduction pathways vs., 785, 785F Phospholipases, 251–252, 251F, 433, 666F Phospholipase A2, 251, 251F, 666F Phospholipase C (PLC), 251, 433, 434 Phospholipids, 251F asymmetric distribution of, 274, 274F diffusion of, in lipid bilayer, 260F formation of lipid bilayers with, 259F in triacylglycerol biosynthesis, 696F Phospholipid translocases, 274, 275 Phosphomannose isomerase, 512 Phosphomevalonate, 708 Phosphomevalonate kinase, 708 N-(Phosphonacetyl)-L-aspartate (PALA), 385 Phosphopantetheine group, 689 Phosphopentose epimerase, 654 Phosphoprotein phosphatase, 390–391 Phosphoprotein phosphatase-1 (PP1), 422, 423, 538–541, 540F Phosphoprotein phosphatase inhibitor (inhibitor 1), 539–541 β-5-Phosphoribosylamine (PRA), 803, 804F, 808 N1-5′-Phosphoribosyl ATP, 757, 757F 5-Phosphoribosyl-α-pyrophosphate (PRPP), 757, 757F, 803, 804F, 808 Phosphoribulokinase, 652 N1-5′-Phosphoribulosylformimino-5-aminoimidazole4-carboxamide ribonucleotide, 757F Phosphorlyase kinase deficiency, 531 Phosphorolysis, 387–388, 524 Phosphorylase, see Glycogen phosphorylase Phosphorylase a, 388, 390F, 538, 539 Phosphorylase b, 388, 538, 539 Phosphorylase kinase, 390, 391, 538, 539, 539F Phosphorylated compounds, 453, 457–460 Phosphorylation See also Oxidative phosphorylation auto-, 409–412 de-, 389–390, 541F of dNDPs, 817 in glycogen metabolism, 541F for glycogen phorsphorylase activation, 538 for phorsphorylase kinase activation, 538, 539 photo-, 458, 650–651 protein, 387–391 substrate-level, 458, 492 Phosphoryl group transfer, 454–455 Phosphoryl group-transfer potentials, 454, 454T 3-Phosphoserine, 752F O-Phosphoserine, 92F Photoautotrophs, 443 Photons, 633, 638, 650–651 Photooxidation, 636, 638–639 Photophosphorylation, 458, 650–651 Photoreactivation, 909–910 Photorespiration, 658–661, 659F Photosynthesis, 6, 7, 479, 630–662 Calvin cycle, 651–658, 653F chemical energy from light energy, 635–636 chloroplasts, 631–635, 631F dark reactions, 651–661 electron transport, 637–650 light reactions, 635–651 net reaction, 630 photophosphorylation, 650–651 and photorespiration, 658–661 two-center electron transport, 639–650 Z-scheme, 641, 641F Photosynthetic bacteria, 633–635, 633F, 637–639 Photosynthetic pigment molecules, 632–635 Photosynthetic reaction centers (RCs), 633, 636F See also Purple photosynthetic bacteria reaction centers (PbRCs) Photosystem I, see PSI Photosystem II, see PSII Phycocyanobilin, 635 Phycoerythrobilin, 635 Phylloquinone, 257, 646, 647 Phylogenetic tree, 9F, 122, 123F, 1042F, 1043 Phylogeny, 9, 122 Phytanate, 716 Phytoplankton, 630 pI, see Isoelectric point PI3Ks (phosphoinositide 3-kinases), 438–439 PIC, see Preinitiation complex Pickart, Cecile, 723 pico- (prefix), 12 Picot, Daniel, 645 Pigments, light-absorbing, 632–635 PII (regulatory protein), 750 Ping Pong reactions, 373 Pioneer polymerase, 961 π orbitals, 736, 736F PIP2 (phosphatidylinositol-4,5-bisphosphate), 434, 434F PIR (Protein Information Resource), 118T PITC (phenylisothiocyanate), 114, 115F Pitch, α helix, 137 Pitch, DNA, 834 PK, see Pyruvate kinase PKA, see Protein kinase A PKB (protein kinase B), 438F PKC (protein kinase C), 436–437 PKM2 (pyruvate kinase), 797 PKU (phenylketonuria), 229, 746 pK values, 34–35, 35T, 82T–83T, 86–87 Placebo, 394 Planar peptide group, 132–135 Planck’s constant, 369, 635 Planck’s constant (h), 12 Planck’s law, 635 Plants, 75, 660–661, 752–757 Plaques, 70, 173, 713, 713F Plasmalogens, 252, 702–703 Plasma membrane, 269F, 282F Plasmids, 67, 929–931 Plasmodium falciparum, 200, 519 Plastocyanin (PC), 641, 645–646, 646F, 649 Plastoquinol (QH2), 640 Plastoquinone (Q), 640, 649 PLC, see Phospholipase C Pleated β sheet, 138, 139F PLP, see Pyridoxal-5′-phosphate PLP-amino acid Schiff base, 736, 736F (+) end, 206, 210 Pmf (protonmotive force), 612 PMP, see Pyridoxamine-5′-phosphate PNP (purine nucleoside phosphorylase), 822 pO2 (partial oxygen pressure), 184, 189–190 Point mutations, 64, 906–907 Pol I (DNA polymerase I): discovery, 883 in DNA sequencing, 57, 57F exonuclease function, 883–885, 884F Klenow fragment, 885F properties, 888T and replication fidelity, 897 Pol II (DNA polymerase II), 887, 888, 888T Pol III (DNA polymerase III): function, 887–888, 888F processivity, 893–895 properties, 888T and replication fidelity, 897 Pol III holoenzyme, 888, 891–895, 893F Pol α (DNA polymerase α), 898, 898T, 899 Polarimeter, 88, 88F Polarity: protein purification by, 102T of side chains, 149–151, 151F of water, 24–27 Polar molecules, 24–27 Polar side chains, 83T, 85–86, 85F, 86F, 150 Pol γ (DNA polymerase γ), 899 Pol δ, 898, 898T, 899, 900F Pol ε, 898, 898T, 899 Pol η (DNA polymerase η), 914 Polpot, Jean-Luc, 645 Poly(A), 985 Poly(C), 985 Poly(Lys), 985 Poly(Phe), 985 I-25 I-26 Index Poly(Pro), 985 Polyacrylamide, 56 Polyacrylamide gel, 857 Polyacrylamide gel electrophoresis (PAGE), 106–107, 107F, 857 Poly(A) binding protein (PABP), 963 Poly(A) binding protein II (PAB II), 962 Polycistronic mRNA, 941 Polyclonal immunoglobins, 214 Polycomb Repressive Complex (PRC2), 1075 Polycythemia, 198 Polyelectrolytes, 103 Polylinker sequence, 67F Polymers, 3, 5T Polymerase α, 898, 898T, 899 Polymerase δ, 898, 898T, 899, 900F Polymerase ɛ, 898, 898T, 899 Polymerase chain reaction (PCR), 71–72, 72F Polymorphic cytochromes P450, 397 Polymorphic genes, 1040 Polymorphisms, 73, 1043 Polynucleotides, 46 Polynucleotide phosphorylase, 985 Polypeptides, 84, 87 conformations, 132–135, 133F disulfide bond cleavage, 112–113 diversity, 98–99 in domains, 154 in protein sequencing, 114, 114F size and composition, 98–99 ubiquitinated, 721–724 Poly(A) polymerase (PAP), 962 Polyproteins, 376 Polyprotic acids, 37, 37F Polyribosomes (polysomes), 1006, 1006F Polysaccharides, 221, 228–234 catabolism, 446F disaccharides, 228, 229 glycosaminoglycans, 232–234 storage, 231–232 structural, 230–231 Polysomes, 1006, 1006F Poly(A) tails, 962–963 Polytopic transmembrane proteins, 280 Polyubiquitin, 720 Polyunsaturated fatty acids, 247, 695 Pompe’s disease, 530 P/O ratios, 618–619 Porcine Sec61, 1028F Pores, 286, 303, 972 Porins, 266–267, 266F, 297, 591, 972 Porphobilinogen (PBG), 758, 759F Porphobilinogen deaminase, 758 Porphobilinogen synthase, 758 Porphyrias, 760 Porphyrin, 182 Positively cooperative binding, 188 Positive regulators, 1046 Postbithorax mutant (pbx), 1091 Postsynaptic membrane, 285 Posttranscriptional control mechanisms, 1069–1076 control of mRNA translation, 1076 lncRNAs, 1075 micro RNAs, 1074–1075 and mRNA degradation rates, 1070, 1071 RNA interference, 1071–1075 Posttranscriptional modification, 961 Posttranscriptional processing, 961–978 5′ capping, 962 intron splicing, 963–972, 978 mRNA, 961–973 rRNA, 973–976 3′ tail for, 962–963 tRNA, 977–978 Posttranslational protein processing, 1024–1029 covalent modifications, 1026–1029 by ribsome-associated chaperones, 1025–1026 for transmembrane proteins, 278–279, 281F Posttranslocational state, 1018, 1019 Potassium (K+) channels, 297–301, 301F Potassium (K+) ion, 296, 297, 335 Poyketides, 694 PP1, see Phosphoprotein phosphatase-1 PP1c, 539, 540 PP2A, 422F, 423 PP2B (calcineurin), 423 PPAR-γ (perioxisome proliferator–activated receptor-γ), 795 PPi, see Pyrophosphate PPM family, 422 PPP family, 422, 423 PRA, see β-5-Phosphoribosylamine Prader-Willi syndrome (PWS), 1063 Pravastatin (Pravachol), 712F pRb protein, 1085 PRC2 (Polycomb Repressive Complex 2), 1075 Prebiotic era, Precursors, Preferential transition state binding, 338–339, 338F Preinitiation complex (PIC): formation of, 957–958, 958F structure of, 960F and transcriptional activators, 1064–1065 Prelog, Vladimir, 90 Pre-miRNAs, 1074, 1075F Pre-mRNAs, 963 Prenylated proteins, 267 Prenyltransferase, 708 Prephenate, 755, 755F Preproproteins, 1026 Preproteins, 278, 278T, 1026 Pre-RC (prereplication complex), 901–902 Prereplication complex (pre-RC), 901–902 Pre-rRNAs, 973–974 Presequences, 278 Pressure, osmotic, 30, 30F Presynaptic membrane, 285 Pretranslocational state, 1018 Pre-tRNAs, 978 Pribnow, David, 942 Pribnow box, 942 Priestley, Joseph, 630 Primaquine, 518, 519 Primary active transport, 310 Primary immune responses, 212F Primary pair-rule genes, 1091, 1092 Primary structure (proteins), 97–126 polypeptide diversity, 98–99 and protein evolution, 119–126 and protein purification and analysis, 99–109 and protein sequencing, 110–119 Primary transcripts, 961 Primase, 882, 891 Primers, 57, 897, 900F Pri-miRNAs, 1074, 1074F Primosome, 891 Prions, 174–175, 174F Prion diseases, 174–175 Prion protein (PrP), 174, 175F Pro, see Proline Probes, colony hybridization, 71 Procarboxypeptidase A, 356 Procarboxypeptidase B, 356 Procaspases, 1086, 1089 Procaspase-9, 1089 Processing body (P body), 1070 Processive enzymes, 883, 893–895, 945 Prochiral molecules, 325 ProCysRS, 994 Product inhibition, 375, 576–577 Products (reaction), 16–18 Proelastase, 356 Proenzymes, 355 Proflavin, 857, 907 Progeria, 905 Progestins, 407 Programmed cell death, 1085–1089 Proinsulin, 1026, 1026F Prokaryotes, 7, 7F classification, DNA economy of, 1039 elongation in eukaryotes vs., 1021 gene number in, 1035T ribosomes, 997–1002 translation initiation in, 1006–1011 Prokaryotic DNA replication, 882–897 DNA polymerases, 883–888, 884F fidelity, 897 initiation, 889–891 leading and lagging strand synthesis, 891–895 termination, 895–897 Prokaryotic gene expression, 1043–1052 attenuation, 1048–1050 catabolic repression, 1046–1048 lac repressor, 1043–1046 repressors, 861–863 riboswitches, 1050–1052 Prokaryotic transcription, 939–948 5′ to 3′ chain growth, 943–946, 944F initiation of, 942–943 RNA polymerase and other polymerases, 939–941 termination of, 946–948 Proliferating cell nuclear antigen (PCNA), 898, 899, 899F Proline (Pro): biosynthesis, 751, 751F, 752 breakdown, 737–738, 737F conformation, 135 nonpolar side chain, 84 Proline racemase, 339 Prolyl hydroxylase, 142 Promoters, 942–943, 954–956 Proofreading, 884, 993–994, 1015 Proofreading site (P), RNAP, 954 Propanolol, 826 Prophospholipase A2, 356 Propionibacterium shermanii, 680, 681F Propionyl-CoA: in amino acid degradation, 738, 739F, 742F from fatty acid oxidation, 678–684, 678F in polyketide synthesis, 694 Propionyl-CoA carboxylase, 678 Propranolol, 405–406 Proproteins, 1026 Prostacyclins, 258 Prostaglandins, 257–258, 695, 704–705 Prostaglandin H2 (PGH2), 258F Prostaglandin H2 synthase, 704 Prosthetic groups, 327 Proteases, 101, 114 Protease inhibitors, 354 Proteasome, 721–724, 722F Protein(s), 80 See also specific proteins allosteric, 195–197 α/β, 153, 154 α, 152–153 α helix, 135–137 from alternative splicing, 969–971 amino acid derivatives in, 91–94 analysis of, 474 assaying, 101 β, 153 catabolism overview, 446F in coated vesicles, 281–282 composition of selected, 99T concentrations of, 101–102 core, 235 covalent modification, 1026–1029 depictions of, 149 DNA–protein interactions, 859–867 dynamics of, 164–165 fibrous, 140–144 folding of, 1025–1026 globular, 140, 149–150 glycosylated, 238–240 heterotrimeric G protein as activator of, 427 homologous, 122 for homologous recombination, 916–922 human genome coding for, 1034–1037 intrinsically disordered, 164–167 isoelectric point, 103, 103T link, 235 Proteins: in lipoproteins, 667–668 Protein(s): membrane, see Membrane proteins motor, 208 multidomain, 126F multisubunit, 98 orthologous, 124 oxygen-transport, 185 possible sequences of, 98 posttranslational modification, 280, 281F prenylated, 267 preproteins, 278, 278T receptor, 402 ribosomal, 1000, 1000F, 1001 Index solubility, 102–103, 102T stabilizing, 100–101 starvation and degradation of, 790–791 thermostable, 162 transport, 293, 305–309 α1-Proteinase inhibitor, 354 Protein crystals, 146–147, 146F Protein Data Bank (PDB), 155–157 Protein degradation, 719–724 lysosomal, 719 proteasome, 721–724, 721F, 722F ubiquitin, 720–721, 720F Protein denaturation, 100, 144, 162–163, 163F Protein design, 167–168 Protein disulfide isomerase (PDI), 168, 169F Protein domains, 125–126, 154, 161–162 Protein evolution, 119–126 comparing structure to study, 157–158 conservation of sequence vs structure, 154–155 gene duplication and gene segments, 122–126 molecular chaperones in, 172 from protein sequences, 120–122 rates of, 125F Protein families, 124 Protein folding, 165–176 diseases from misfolding, 173–176 energy-entropy diagram, 166F molecular chaperones in, 168–172 pathways, 165–168, 166F unfolded regions of proteins, 164–165 Protein function, 180–218 of antibodies, 212–217 information from sequence comparisons on, 122 muscle contraction, 200–211 oxygen binding, 181–200 and structure, 97 Protein Information Resource (PIR), 118T Protein kinases, 252, 387, 390–391 Protein kinase A (PKA), 427–431, 429F, 538 Protein kinase B (PKB), 438F Protein kinase C (PKC), 436–437 Protein mass fingerprinting, 117 Protein misfolding diseases, 173–176, 173T Protein phosphatases, 253, 387, 420–423 Protein phosphorylation, 387–391 Protein purification, 99–109, 102T chromatography, 103–106 electrophoresis, 106–108 by solubility, 102–103 strategy for, 100–102 ultracentrifugation, 108–109 Protein renaturation, 163–164, 163F Protein scaffold (metaphase chromosomes), 872–874 Protein sequences: divergence rate for, 124–125 evolutionary relationships revealed by, 120–122 and secondary structure, 144–145 storage of, 118–119 Protein sequencing, 110–119, 111F database storage of sequences, 118–119 Edman degradation, 114–116, 115F mass spectrometry, 117–118 polypeptide cleavage, 114 separating subunits, 110–113 Protein Ser/Thr phosphatases, 422, 423 Protein stability, 160–165 denaturation and renaturation, 162–164 forces involved, 160–162 and protein dynamics, 164–165 Protein structure(s): bioinformatics, structural, 155–158, 156T conservation of, 154–155 information from sequence comparisons on, 122 nonrepetitive, 144–145 and oligosaccharides, 240–241 predicting, 167–168 primary structure, 97–126 and protein folding, 165–176 quaternary structure, 132, 132F, 158–159 secondary structure, 132–145, 132F and stability, 160–165 supersecondary, 151–152, 151F symmetry, 159, 159F tertiary structure, 131, 132F, 145–158 Protein synthesis, 982–1030 chain elongation, 1005, 1011–1022 chain initiation, 1006–1011 chain termination, 1023–1024 genes as directors of, 51–53 and genetic code, 983–988 heme-controlled, 1076F posttranslational processing, 1024–1029 by recombinant DNA techniques, 72, 73, 73T ribosomes, role of, 938 and ribosomes, 996–1004, 1011–1022 translation, 1004–1024 translation initiation, 1009F and tRNA, 988–996 Protein tyrosine kinases (PTKs), 409, 420 Protein tyrosine phosphatases (PTPs), 421–423 Proteoglycans, 235, 235F Proteolysis, 114 Proteome, 53, 471, 474 Proteomics, 53, 108, 474 Proteopedia, 157 Prothrombin, 356 Protofilaments, 141F Protomers, 158 Protons: acids as donors of, 33 and ATP synthase, 613–618 as electrophiles, 335F translocation by Complex I, 599–601 translocation by Complex III, 602–607 translocation by cytochrome c oxidase, 609–610 Proton gradients, 316–318 and ATP synthesis by photophosphorylation, 650–651 from electron transport in cytochrome b6f, 645 in light reactions, 648–651 in oxidative phosphorylation, 611–613 and PSI-activated electrons, 648–649 Proton jumping, 32, 32F Protonmotive force (pmf), 612 Proton pumps, 600, 600F Protonpumping ATP synthase, see ATP synthase Proton wire, 600 Proto-oncogenes, 416 Protoporphyrin IX, 602, 759, 759F Protoporphyrinogen IX, 759F Protoporphyrinogen oxidase, 759 Protospacers, 925, 926 Protosterol, 710, 711F Proximity effects (enzymes), 336–338 PrP (prion protein), 174, 175F PrPC (cellular prion protein), 174 PRPP, see 5-Phosphoribosyl-α-pyrophosphate PrPSc (scrapie form of prion protein), 174, 176 Pruisner, Stanley, 174 PSI (photosystem I), 639–641 cofactors of, 647F electron pathways, 648–650 electron transport by plastocyanin to, 645–646 and PSII, 646–650 segregation, 649 X-ray structure, 646F PSII (photosystem II), 639–643 PbRC and reaction center of, 641–643, 646–648 and PSI, 646–650 segregation, 649 of T elongatus, 642F PsaA, 646 PsaB, 646 PsaC, 647F PsaC–E, 646, 648 PsaF, 646 PsaI–M, 646 PsaX, 646 PsbA (D1), 641 PsbB (CP47), 641 PsbC (CP43), 641 PsbD (D2), 641 Pseudo-first-order reaction, 364 Pseudogenes, 124, 1038 Pseudomonas aeruginosa, 234F Pseudouridine (ψ), 968F, 974, 988, 989F ψ angles, 133, 134 D-Psicose, 223F P (peptidyl) site, 1001, 1002 PTC (phenylthiocarbamyl), 114, 115F Pteridine, 745, 745F Pterins, 745, 745F, 746 I-27 Pterin-4a-carbinolamine, 746 Pterin-4a-carbinolamine dehydratase, 746, 747F PTH (phenylthiohydantion), 115F, 116 PTKs (protein tyrosine kinases), 409, 420 PTPs (protein tyrosine phosphatases), 421–423 P-type ATPases, 310 pUC18 plasmid, 67–69, 67F Pulmonary emphysema, 354 Pulsed-field gel electrophoresis (PFGE), 857, 857F Pulse-labeling, 881 Pumped protons, 609 PurE, 805 Pure noncompetitive inhibition, 382 Purines, 43, 839F Purine derivatives, 826 Purine nucleoside phosphorylase (PNP), 822 Purine nucleotide cycle, 823 Purine ribonucleotides, 808, 822–825, 822F Purine ribonucleotide synthesis, 802–809, 804F AMP, 806–807 GMP, 806–807 and IMP, 803–807, 804F regulation of, 807–808, 807F PurK, 805 Puromycin, 1020 Purple photosynthetic bacteria reaction centers (PbRCs): electron transport in, 637–638, 637F and PSI, 646–648 and PSII, 641–643, 646–648 PWS (Prader-Willi syndrome), 1063 Pyl (Pyrrolysine), 996 PylRS, 996 Pyocyanin, 627 Pyran, 224 Pyranoses, 224 Pyridine nucleotides, 326F Pyridoxal-5′-phosphate (PLP): as covalent catalyst, 335 forms of, 725F as glycogen phosphorylase cofactor, 526 and serine hydroxymethyltransferase, 735–736 in transamination, 725–727, 727F Pyridoxamine-5′-phosphate (PMP), 725F, 726, 727F Pyridoxine, 526, 725, 725F Pyrimidine, 43, 839F Pyrimidine dimers, 905 Pyrimidine ribonucleotides, 827, 827F Pyrimidine ribonucleotide synthesis, 384F, 809–812 CTP, 811, 811F regulation, 811–812 UMP, 809–811, 809F UTP, 811, 811F Pyrithiamine, 1052 Pyrithiamine pyrophosphate, 1052 Pyrobaculum aerophilum, 967 Pyrolobus fumarii, 162 Pyrophosphatase, 457 Pyrophosphate (PPi ), 57F, 454, 454T Pyrophosphate cleavage, 457, 457F 5-Pyrophosphomevalonate, 708 Pyrophosphomevalonate decarboxylase, 708 Pyrorline-5-carboxylate, 737F Pyrosequencing, 60 Pyrrole, 182 Pyrrole-2-carboxylate, proline racemase inhibition, 339 Δ-1-Pyrroline-2-carboxylate, 339 Δ1-Pyrroline-5-carboxylate, 751F, 752 Pyrroline-5-carboxylate reductase, 752 Pyrrolysine (Pyl), 996 Pyruvate, 456F alcoholic fermentation of, 498–501 amino acid biosynthesis from, 581, 748–749, 748F, 754–755, 754F in amino acid degradation, 733F–735F, 734–736 in citric acid cycle, 560F, 563–565, 565F, 577 in gluconeogenesis, 545–549, 545F, 546F, 581 in glucose–alanine cycle, 781 in glycolysis, 494–497 homolactic fermentation of, 498 isozyme action of, 449 and malic enzyme, 683 in mammalian metabolism, 775 metabolic fate of, 497, 497F in tricarboxylate transport system, 688F I-28 Index Pyruvate carboxylase, 546–547, 547F Pyruvate decarboxylase, 499–500, 500F Pyruvate dehydrogenase (E1), 563F in citric acid cycle, 562–567 coenzymes and prosthetic groups, 564T and α-ketoglutarate dehydrogenase, 572 reactions of, 565F regulation of, 576–577, 576F Pyruvate dehydrogenase kinase, 576 Pyruvate dehydrogenase phosphatase, 576 Pyruvate enolate, 547F Pyruvate:ferredoxin oxidoreductase, 583 Pyruvate kinase (PK): in coupled reactions, 456 in glycolysis, 494–497, 503 mechanism of, 495F PKM2, 797 Pyruvate-phosphate dikinase, 661 Pyruvic acid, 226 PYY3-36, 789 q (heat), 12, 15 Q (plastoquinone), 640, 649 Q6, 598 Q8, 598 Q10, 598 Q cycle, 602–607, 605F QH2 (plastoquinol), 640 qP (heat at constant pressure), 12 Q-SNAREs, 285, 286 Quanta, 635 Quantum yield, 638 Quaternary structure (proteins), 132, 132F, 158–159 Quinine, 391, 391F Quinod form, 7,8-dihydrobiopterin, 746, 747F Quinol oxidase, 612 R (gas constant), 12 R5P, see Ribose-5-phosphate Rabbit: G-actin, 205F glycogen phosphorylase, 388F muscle phosphorylase kinase, 539F Racemic mixtures, 90 Racker, Efraim, 613 Rad51, 920 Radioactive isotopes, 469, 469T Radioimmunoassay (RIA), 101, 404 Radionuclides, 469, 469T Raff, Martin, 1086 Raf kinase, 415 RAG1, 1079 RAG2, 1079 Ramachandran, G N., 134 Ramachandran diagram, 134–135, 135F Ramakrishnan, Venki, 999, 1013, 1024 Randall, John, 833 Randle, Phillip, 623 Randle cycle (glucose-fatty acid cycle), 623 Random coils, protein, 144 Random mechanism, sequential reactions with, 372, 373 Randomness, of genetic code, 986 Rapamycin, 438F Ras, 412–414, 413F RasGAP, 414, 415 Ras signaling cascade, 413F, 785, 785F, 1069 Rat: intestinal fatty-acid binding protein (I-FABP), 666, 667F liver enzymes half-lives, 719, 719F liver mitochondrion, 590F liver peroxisome, 684F PFK-2/FBPase-2, 550F rat liver cytoplasmic ribosomes, 1002, 1003T testis calmodulin, 434F Rat1 (Xrn2), 963 Ratcheting, 1021 Rate constant (k), 362, 364 Rate-determining step, 329 Rate enhancement, 329–330 Rate equations, 362–364 Rational drug design, 392 Ratner, Sarah, 729 Rayment, Ivan, 203, 731 RCs, see Photosynthetic reaction centers Reactants, 16–18 Reaction conditions, 323 Reaction coordinate diagram, 327–330, 328F, 329F Reaction kinetics, see Enzyme kinetics Reaction mechanism, steady state kinetics and, 371–373 Reaction order, 362–363 Reaction rate, for enzymes vs chemical catalysts, 323 Reactive oxygen species (ROS), 602, 624, 625 Reads (DNA sequences), 59 Readers, 1059 Reading frame, 983–984 Rearrangements, 448, 931, 933, 933F RecA5–(ADP–AlF4-)5–(dT)15(dA)12 complex, 918, 918F, 919 RecA-mediated pairing, 919, 919F RecA-mediated strand exchange, 919–920, 920F RecA protein, 915, 917–920, 918F, 920F RecBCD protein, 920–921, 920F, 921F Receptors, 402 See also specific receptors Receptor–ligand binding, 407, 410 Receptor-mediated endocytosis, 287, 288, 670–671, 670F Receptor tyrosine kinases (RTKs), 408–423 and kinase cascades, 412–417 and nonreceptor tyrosine kinases, 417–420 and protein phosphatases, 420–423 signal transmission by, 409–412 Recognition events, 241 Recombinant DNA, 67, 69F Recombinant DNA technology, 66, 69F, 72–76 Recombination, 64, 916–933 and CRISPR–Cas9 system, 925–929 homologous, 916–922, 916F repair by, 922–925, 923F, 924F somatic, 1078–1079 transposition, 64, 929–933 Recombination repair, 922–925, 923F, 924F Recombination signal sequences (RSS), 1077, 1079, 1079F Recommended name, 324 Recruitment model for transcription factors, 1065 Red blood cells, see Erythrocytes Redox centers, 588, 607F, 765–766 Redox cofactors, 602 Redox couples, 463 Redox reactions, see Oxidation–reduction reactions Reduced (term), 446 Reducing agents, 463 Reducing end, 232 Reducing equivalents, 548–549, 591–592 Reducing sugars, 227 Reductant, 463 Reduction, 447 See also Oxidation–reduction reactions with nitrogen, 767–768, 767F of oxygen, 607–609, 618–619, 624, 625 of ribonucleotide reductases, 814–816 Reduction potential, 465–467 Reductive pentose phosphate cycle, see Calvin cycle Rees, Douglas, 765 Regeneration, 327, 458–459 Regular secondary structures (proteins), 135–140 Regulatory light chains (RLC), 203, 204 Regulatory proteins, 1063–1064 Reichard, Peter, 813 Relative configuration, 89, 90 Relative molecular mass (Mr), 12 Relaxed circles, 840F, 841 Release factor (RF), 1008T, 1023–1024 Remington, James, 569 Renaturation: DNA, 852, 852F protein, 163–164, 163F Reperfusion injury, 183 Repetitive DNA sequences, 1039–1043 Replica plating, 71 Replicases, 887, 888 Replication See also DNA replication of linear chromosomes, 902, 902F of molecules, 3, 5F of transposons, 931 Replication eye, 881F Replication factor C (RFC), 899 Replication forks, 881, 897, 902, 922, 923F Replication protein A (RPA), 899 Replicative transposons, 931 Replicons, 902 Replisome, 891, 894F Reporter genes, 93 Repressors, 862F corepressors, 1048 lac, 1043–1046, 1045F, 1046F, 1048 met, 862, 863, 863F prokaryotic, 861–863 trp, 862, 863F RER, see Rough endoplasmic reticulum Resequencing, 65, 66 Resistin, 795 Resolution, of protein crystals, 146–147, 147F Resolvase, 931 Resonance, bond, 455 Resonance energy transfer, 636 Resonance-stabilized intermediates, 727F Respiration, 479 Respiratory distress syndrome, 251 Restart primosome, 924 Restriction endonucleases: DNA–protein interactions, 860–861, 861F for nucleic acid sequencing, 54–56 recognition and cleavage sites, 55T Restriction–modification system, 54 Restriction sites, 55F Reticulocyte heme-controlled protein synthesis, 1076 Reticulocytes, 760, 1004, 1076, 1076F Retinal, 257, 600 Retinoblastoma, 1085 Retinol, 257 Retinol binding protein, 153F Retro aldol condensation, 485 Retrograde transport, 280 Retrotransposons, 933 Retroviruses, 900–901, 933 Reverse transcriptase (RT), 70, 376, 899–901 Reverse turns, 140, 140F Reversible processes, 14, 450 RF (release factor), 1008T, 1023–1024 RF-1, 1023 RF-2, 1023 RF-3, 1023 RFC (replication factor C), 899 R groups, amino acids, 81 Rhamnose, 234 Rhizobium, 764F, 768 Rhodobacter sphaeroides, 637, 637F Rhodopseudomonas viridis, 637, 637F Rhodopsin, 424 Rhodospirillum molischianum, 634, 634F Rho factor, 947–948, 948F RIA (radioimmunoassay), 101, 404 Ribitol, 226 Riboflavin (vitamin B2), 463, 463F Ribonucleases, see specific RNases Ribonucleic acid, see RNA Ribonucleoproteins, 902, 1026–1028 Ribonucleotides, 43, 43F, 812–817 See also specific types Ribonucleotide reductases (RNRs), 812–817 and phosphorylation of dNDPs, 817 reduction by thioredoxin, 814–816, 815F regulation of, 816, 817F structure, 813F substrate binding by, 814 tyrosyl radicals and, 608 Ribose, 43, 222F, 223 Ribose-5-phosphate (R5P): in Calvin cycle, 653F, 654 in IMP synthesis, 803, 804F in pentose phosphate pathway, 513F, 514, 515, 516F Ribose phosphate isomerase, 654 Ribose phosphate pyrophosphokinase, 803 Ribosomal proteins, backbone structures of, 1000, 1000F, 1001 Ribosomal RNA, see rRNA Ribosomes, 996–1004 binding sites of, 1019F in chain elongation, 1011–1022 decoding, 1011–1013, 1014F distribution of protein and RNA in, 1000, 1000F and EF-G, 1018, 1018F and elongation in prokaryotes vs eukaryotes, 1021 as entropy trap, 1016–1017 Index eukaryotic, 1002–1004 membrane protein synthesis in, 276–280 monitoring of codon–anticodon pairing by, 1013–1014 prokaryotic, 997–1002 proofreading by, 1015 in protein synthesis, 52–53 and SRP, 1027F structure of, 997–1001, 998F translocation in, 1017–1021 and transpeptidation, 1015–1016 with tRNA and mRNA, 1001F tRNA binding sites of, 1001–1002 Ribosome recycling factor (RRF), 1023–1024, 1023F, 1024F Riboswitches, 1050–1052 Ribozymes, 20 enzymatic activity, 322–323 hammerhead, 853–856, 855F Tetrahymena species, 975–976, 976F Ribulose, 223, 223F D-Ribulose, 223F Ribulose-1,5-bisphosphate (RuBP), 652, 659F Ribulose-5-phosphate (Ru5P), 513F, 514, 515F, 651, 653F Ribulose-5-phosphate epimerase, 515 Ribulose-5-phosphate isomerase, 515 Rice, golden, 75, 75F Rich, Alexander, 835, 853 Richmond, Timothy, 869 Ricin, 1021 Rickets, 256 Rieske, John, 604 Rieske center, 604 Rifampicin, 950 Rifamycin B, 950 Rigor mortis, 219 RING finger, 720, 721 Rinn, John, 1075, 1083 RISC, see RNA-induced silencing complex Ritonavir, 377, 397 Rittenberg, David, 469, 687, 758 RLC (Regulatory light chains), 203, 204 RNA (ribonucleic acid): A-DNA type helix formation, 836, 838 catalytic properties, 323 DNA–RNA hybrids, 838, 838F human genome transcribed to, 1037 hybridization, 852 metabolite-sensing, 1050–1052 nucleotides, 44 single-stranded nucleic acids in, 50 structure of, 852–856 synthesis of, 52–53 as telomere template, 902–904 RNA-dependent RNA polymerase, 1073 RNA–DNA hybrids, 852 RNA editing, 971–972 RNAi (RNA interference), 1071–1075, 1072F RNA-induced silencing complex (RISC), 1073, 1074, 1074F RNA interference (RNAi), 1071–1075, 1072F RNA ligase, 978 RNAP, see RNA polymerase RNAP I (RNA polymerase I), 949, 954 RNAP II, see RNA polymerase II RNAP III, see RNA polymerase III RNAP II-Mediator complex, 1065–1066, 1065F RNA polymerase (RNAP), 939 chain growth, 943–946, 944F collisions of DNA polymerase and, 945 eukaryotic, 949–956 as processive enzyme, 945 prokaryotic, 939–948 promoter recognition and binding by, 942–943, 954–956 proofreading by, 953–954 structure, 939–941, 939F, 940F, 951–953 transcription termination sites, 946–948 RNA polymerase I (RNAP I), 949, 954 RNA polymerase II (RNAP II), 949–953 and elongation, 961 promoters for, 954–955, 955F structure and function of, 951–953, 952F, 953F TFIIA and TFIIB interaction with, 958–960 RNA polymerase III (RNAP III), 949, 954, 956 RNA polymerase holoenzyme, 939, 939F, 940F, 942, 943 RNA primers, 882, 884F, 891, 897, 900F RNA-recognition motifs (RRM), 971 RNase III, 973, 1073 RNase A (ribonuclease A), 163–164, 163F, 332–334, 333F RNase B, 240F RNase D, 973 RNase E, 973 RNase F, 973 RNase H, 892, 893 RNase H1, 899, 900F RNase M5, 973 RNase M16, 973 RNase M23, 973 RNase P, 973, 977, 977F RNase S (ribonuclease S), 332F RNA triphosphatase, 962 RNA world, 50, 854 RNRs, see Ribonucleotide reductases Roberts, Jeffrey, 947 Roberts, Richard, 963, 964, 1061 Rodnina, Marina, 1016 Rofecoxib (Vioxx), 392, 395, 705 ROS, see Reactive oxygen species Rose, Irwin, 484, 720 Rose, William C., 81 Rosenberg, John, 860 Rosetta program, 167 Rosiglitazone (Avandia), 395, 795 Rossmann, Michael, 154 Rossmann fold, 154 Rotational symmetry (proteins), 159 Rotenone, 595, 596 Rothman, James, 274, 285 Rough endoplasmic reticulum (RER), 274F, 277, 448F Rous sarcoma virus (RSV), 416 RPA (replication protein A), 899 Rpb1 subunit, 950, 951, 961 Rpb2 subunit, 952 Rpr4, 1071 Rpr6, 1071 Rpr40, 1071 Rpr41, 1071 Rpr42, 1071 Rpr43, 1071 Rpr44, 1071 Rpr45, 1071 Rpr46, 1071 RRF, see Ribosome recycling factor RRM (RNA-recognition motifs), 971 rRNA (ribosomal RNA), 52, 938 base pairing of mRNA and, 1006–1007 double-stranded segments, 853 posttranscriptional processing, 973–976 secondary structure of, 997, 998, 998F self-splicing, 974–975, 974F tertiary structure, 999F RSC complex, 1054, 1054F RS domain, 971 R-SNAREs, 285, 286 RSS, see Recombination signal sequences RS (Cahn–Ingold–Prelog) system, 90 R state: of glycogen phosphorylase, 389, 389F, 390, 390F of hemoglobin, 190–192, 196, 197 RSV (rous sarcoma virus), 416 RT, see Reverse transcriptase RTKs, see Receptor tyrosine kinases Rtt103, 963 Ru5P, see Ribulose-5-phosphate RuBisCO, 658 RuBP (ribulose-1,5-bisphosphate), 652, 659F RuBP carboxylase, 654–655, 654F, 655F, 657 RuBP carboxylase activase, 655 RuBP carboxylase-oxygenase, 658, 658F Rudder, 953 runt gene, 1091 Rut sites, 947 Rutter, William, 1064 RuvA protein, 921–922, 921F, 922F RuvB protein, 921–922 RuvC protein, 922 I-29 S, see Entropy S (svedbergs), 109, 721 S1P (site-1 protease), 712 S2P (site-2 protease), 712 S4 helix, 301 S5 helix, 301 S6′, 723 S6 helix, 301 S6 protein, 438F S7P, see Sedoheptulose-7-phosphate Sabatini, David, 277 Saccharides, 221 See also Carbohydrates Saccharine, 229 Saccharomyces cerevisiae, 100, 995 Saccharomyces uvarum, 499F Saccharopine, 743, 743F Saccharopolyspora erythraea, 694 Saenger, Wolfram, 642 SAGA, 1057 SAICAR (5-aminoimidazole-4-(N-succinylocarboxamide) ribotide), 797, 804F, 805 Saiety, 788–789 Salmonella typhimurium, 303F, 749F, 756, 756F, 907 Salts, solvation in water, 27 Salt bridge, 161 Salting in, 102 Salting out, 102–103, 102F Salvage pathways, 808 SAM, see S-Adenosylmethionine Sanger, Frederick, 57, 110, 112, 680, 964 Santi, Daniel, 818 Sarcomas, 416, 1083 Sarcomere, 201 Sarcoplasmic reticulum, 208, 313 Sarcosine, 771 Sarin, 346 Saturated enzymes, 367 Saturation, 184, 247–248, 247T, 308, 367 Sazanov, Leonid, 597, 601 SBP (sedoheptulose-1,7-bisphosphate), 653F SBPase, see Sedoheptulose-1,7-bisphosphatase Scaffolds, metaphase chromosome, 872–874 Scaffold proteins, 416–417 Scalar protons, 609 SCAP (SREBP cleavage-activating protein), 711, 711F Scatchard, George, 410 Scatchard plot, 410 Schachman, Howard, 383 Schekman, Randy, 285 Schiff bases: formation (transimination), 725, 726 imines as, 331, 334, 334F, 335F PLP-amino acid, 736, 736F Schistosoma mansoni, 854, 855 Schulz, Georg, 460 SCID (severe combined immunodeficiency disease), 76, 823 SCID-X1, 76 SCOP (computer program), 158 Scott, Matthew, 1093 Scott, William, 855 Scrapie, 174 Scrapie form of prion protein (PrPSc), 174, 176 Screening, DNA, 65, 65T, 71 Scr protein, 412 Scrunching, 945 Scurvy, 142, 143 SDS (sodium dodecyl sulfate), 107 SDS-PAGE (sodium dodecyl phosphatepolyacrylamide gel electrophoresis), 107, 107F Sec (selenocysteine), 996 Sec61, 279, 1028, 1028F Secondary active transport, 310 Secondary channel, Rpb2, 952 Secondary immune responses, 212F Secondary lysosome, 670F Secondary pair-rule genes, 1092 Secondary structure (proteins), 131–145, 132F α helix, 135, 137 β sheet, 138–140 of fibrous proteins, 140–144 nonrepetitive, 144–145 planar peptide group of, 132–135 regular, 135–140 and sequence, 144–145 super-, 151–152, 151F in tertiary structure, 150–154 I-30 Index Second law of thermodynamics, 13 Second messengers, 424 activation of protein kinase C by, 436–437 cytoplasmic release of, 433–434 and glycogen metabolism, 542 phosphodiesterases and activity of, 432 in signaling pathways, 402 Second-order reactions, 362–364 Secreted membrane proteins, 277–279, 281–282 Secretory pathway, 276–280, 277F Secretory vesicles, 281F SecY, 279–280, 279F, 1028 Sedoheptulose-1,7-bisphosphate (SBP), 653F Sedoheptulose bisphosphatase (SBPase), 652, 654, 657, 658, 658F Sedoheptulose-7-phosphate (S7P), 513F, 516, 516F, 517F, 653F Seed sequence, 1074 Segmental duplications (DNA), 1040 Segmentation genes, 1090 Segment polarity genes, 1091 SELB, 996 Selectable markers, 69 Selectins, 241 Selection, for cloned DNA, 68–70 Selectivity filters, 298F, 299, 303 Selenocysteine (Sec), 996 Selenoproteins, 996 Self-comparmentalized proteases, 723–724, 724F Selfish DNA, 1042 Self-replicating systems, 3–5 Self-splicing rRNA, 974–975 Sem-5 protein, 414 Semiconservative replication, 879, 880 Semidiscontinuous replication, 881–882, 881F Semi-invariant positions (tRNA), 989 Semiquinone, 463F Senescence, 905 Sense RNA, 1071 Sense (coding) strand, 941, 941F, 942, 942F Sequence-specific DNA-binding proteins, 859, 860 Sequencing-by-synthesis methods, 59–61 Sequential model of allosterism, 196–197, 197F Sequential reactions, 372–373 Serine (Ser): biosynthesis, 752, 752F breakdown, 734–735, 734F in ceramide biosynthesis, 704F covalent catalysis by, 335 genetic code specification, 985, 986 and N5,N10-methylene-THF, 819F and O-linked oligosaccharides, 240 phosphatidylserine from, 702 in photorespiration, 659F in sphingolipid synthesis, 703–704 and THF, 741F uncharged polar side chain, 85, 85F Serine carboxypeptidase II, 349F Serine hydroxymethyltransferase, 735–736, 820 Serine proteases, 345–358 active site, 345–346, 349F catalytic mechanism, 350–355, 351F preferential transition state binding, 350, 352, 352F specificity pockets, 348F X-ray structure, 346–350 zymogens, 355–357 Serine–threonine dehydratase, 734, 735F Serotonin, 424, 762 Serum albumin, 671 Serum glutamate-oxaloacetate transaminase (SGOT), 726 Serum glutamate-pyruvate transaminase (SGPT), 726 SET7/9, 1060, 1060F SET domain, 1060 7S RNA, 1027F 70S ribosome, 997T Severe combined immunodeficiency disease (SCID), 76, 823 Sex hormones, 406–407 SGOT (serum glutamate-oxaloacetate transaminase), 726 SGPT (serum glutamate-pyruvate transaminase), 726 sgRNA (single-guide RNA), 926–929, 927F sgRNA–Cas9 system, 927–929 SH2 domains, 412, 412F, 418–419, 969 SH3 domains, 148F in kinase cascades, 412, 414, 414F splicing and evolution of, 969 of Src, 418–419 Sharp, Phillip, 963, 964 Shc protein, 438 Shear degradation, 868 Shemin, David, 469, 758 Shen, Jian-Ren, 644 Shine, John, 1007 Shine–Dalgarno sequence, 1007 Short interfering RNAs (siRNAs), 1072 Short interspersed nuclear elements (SINEs), 1042 Short tandem repeats (STRs), 73, 1040 Short-term regulation, 698 Shotgun cloning, 70 Shotton, David, 347 SHP-2, 421, 421F, 438F Shulman, George, 794 Sialic acid, 227 Sickle-cell anemia, 61, 198–199, 200F, 519 Sickle-cell hemoglobin (hemoglobin S), 198–200 Side chains, amino acid, 84–86 charged polar, 83T, 86, 86F, 150 hydropathy, 160T modifications of, 92, 92F nonpolar, 82T, 84, 85F, 149 polarity and location of, 149–151, 151F uncharged polar, 83T, 85, 85F, 150 SIDS (sudden infant death syndrome), 675 Sigler, Paul, 170, 426, 862, 957, 1069 σ32, 943 σ70, 943 σ factor, 943 σgp28, 943 σgp33/34, 943 Sigmoidal binding curve, 188, 188F Signal-anchor sequences, 280 Signal-gated channels, 300 Signal peptidase, 278 Signal peptides, 277, 278 Signal recognition particle (SRP), 278, 1026–1028, 1027F Signal recognition particle receptor, 278 Signal strength, 301 Signal transduction: hormones for, 408 in metabolic regulation, 785–786, 785F and non-insulin-dependent diabetes mellitus, 793–795 and transcription factors, 1066 Signal-transduction pathways, 1069 Signature sequence (TVGYG), 299 Signer, Rudolf, 833 Sildenafil, 432 Simian virus 40 (SV40), 842F, 955 Simmons, Daniel, 705 Simvastatin (Zocor), 712F SINEs (short interspersed nuclear elements), 1042 Singer, S Jonathan, 269 Single blind tests, 394 Single-displacement reactions, 372–373 Single-guide RNA (sgRNA), 926–929, 927F Single nucleotide polymorphisms (SNPs), 65, 1037 Single-strand binding protein (SSB), 891, 891F Single-stranded DNA (ssDNA), 880 Single-stranded nucleic acids, 50 siRNAs (short interfering RNAs ), 1072 Site-1 protease (S1P), 712 Site-2 protease (S2P), 712 Site-directed mutagenesis, 73–74, 74F Site-specific recombination, 916 SI units, 12 6dEB (6-deoxyerthythronolide B), 694 16S rRNA, 973, 997, 999, 1006–1007 60S subunit, 1002, 1003T Size exclusion chromatography, 105 Skehel, John, 288 Skeletal muscles, see Muscle Ski7p protein, 1070 Skou, Jens, 310 Slack, Rodger, 660 SLI, 960 Slicer, 1073 Sliding clamp, 893–895, 893F Sliding filament model, 202, 203 Slow-twitch muscle fibers, 502 Small intestine, 666–667 Small nuclear ribonucleoproteins (snRNPs), 966–967 Small nuclear RNA (snRNA), 966 Small nucleolar RNA (snoRNA), 973–974 Small ribosomal subunit, 997, 997T, 999–1002, 1003T Small ubiquitin-related modifier (SUMO), 1026 Smith, Cassandra, 857 Smith, Emil, 120 Smith, Janet, 645 Smith, Michael, 73 Smooth endoplasmic reticulum, 274F, 448F Sm proteins, 967, 967F Sm RNA motif, 967 SN2 reaction, 337, 337F SNAP-25, 285F SNAREs, 285–287, 285F, 287F Snell, Esmond, 726 snoRNA (small nucleolar RNA), 973–974 SNPs (single nucleotide polymorphisms), 65, 1037 snRNA (small nuclear RNA), 966 snRNPs (small nuclear ribonucleoproteins), 966–967 snRNP core protein, 967 SOD (superoxide dismutase), 625–626, 625F Sodium (Na+) channels, 300, 301 Sodium dodecyl phosphatepolyacrylamide gel electrophoresis (SDS-PAGE), 107, 107F Sodium dodecyl sulfate (SDS), 107 Sodium (Na+) ion, 297, 301, 335, 850 Sodium–potassium ATPase, see (Na+–K+)–ATPase Sodium–potassium (Na+–K+) pump, 310–312 Soft keratins, 141 Solubility, protein purification by, 102–103, 102T Soluble protein factors, 1007–1010, 1008T Solvation, 27, 27F Solvent, water as, 27 Somatic hypermutation, 217, 1079–1080 Somatic recombination, 216, 1078–1079 Somatostatin, 404 Sonication, 59, 627 D-Sorbose, 223F Sørenson, Søren, 32 Soret bands, 602 Sos protein, 414 SOS response, 915 Southern, Edwin, 858 Southern blotting, 858–859 Sowadski, Janusz, 428 spCas9 protein, 926, 927F Special pair, 637–639 Specificity: of enzymes vs chemical catalysts, 323, 324 geometric, 325–326 ion, 299, 299F of mediated vs nonmediated transport, 308 protein purification by, 102T of serine proteases, 348–349, 349F stereo-, 325 Specificity site, 816, 817F Spectrin, 272, 272F Spectroscopy, 101–102, 148, 148F Speed, of mediated vs nonmediated transport, 308 S phase, 1080, 1081 Sphinganine, 704, 704F Sphingoglycolipids, 703–704 Sphingolipids: and amino alcohols, 252–253 degradation, 706, 707 structure, 700F synthesis, 703–704 Sphingolipid storage diseases, 253, 706 Sphingomyelins, 252–253, 252F, 704, 706 Sphingophospholipids, 252 Sphingosine, 252, 253F Spina bifida, 740 Splenda®, 229 Spliceosome, 966–967 Splicing, 963–972, 966F, 978 Spontaneity, 11, 14–15, 465–467 Spontaneous processes, 12, 13 Sprang, Stephan, 426 Squalene, 708–710, 709F Squalene epoxidase, 710 Squalene synthase, 709, 709F Squelching, 1065 SR-BI, 671 Src (protein), 148F Index Src activation, 419, 419F Src ∙ AMPPNP, 418, 418F Src family, 418–419 Src homology domains, see SH2 domains; SH3 domains SRE (sterol regulatory element), 711 SREBP, see Sterol regulatory element binding protein SREBP cleavage-activating protein (SCAP), 711, 711F SRP, see Signal recognition particle SRP9, 1027 SRP14, 1027 SRP19, 1027 SRP54, 1027, 1028 SRP68, 1027 SRP72, 1027 SRP receptor, 278 SR proteins, 971 SSB (single-strand binding protein), 891, 891F ssDNA (single-stranded DNA), 880 Ssl2, 959 Stacking interactions: DNA, 849, 850, 850F, 850T RNA, 853, 853F Stadtman, Earl, 749 Stahl, Franklin, 879, 880F Standard reduction potential (ℰo′), 465–466, 466T Standard state, 16–18 Staphylococcus aureus, 236, 993F Starch, 231–232, 655–656, 656F Starch synthase, 655, 656 Start codons, 986, 987 Starvation, 790–792 Stat3β, 1068, 1068F State functions, 15 Statins, 712–713 Stationary phase, in chromatography, 103–106 STATs, 1066–1068 Ste5p, 417 Steady state: and enzyme kinetics, 364–367, 371–373 and mammalian fuel metabolism, 775 and metabolic pathways, 450 non-equilibrium, 19–20 Steady state assumption, 364–367 Stearic acid, 246, 246F, 253F 1-Stearoyl-2-oleoyl-3-phosphatidylcholine, 250F Steitz, Joan, 966 Steitz, Thomas, 885, 992, 993, 999 Stem–loop structures, 50, 50F Stercobilin, 761, 761F Stereochemistry, 88–91 Stereoelectronic control, 488 Stereoisomers, 89, 90 Stereospecificity, 325, 325F Steric interference: in DNA, 838–840, 838F, 839F of peptide groups, 134F Steroids, 254–256, 406–407 Steroid hormones, 254–255, 255F Steroid receptors, 406, 1068 Sterols, 254 Sterol regulatory element (SRE), 711 Sterol regulatory element binding protein (SREBP), 711, 711F, 1066 Sterol-sensing domain, 711 Stevia, 229 Sticky ends, 55, 846 Stigmatellin, 604F, 606 Stop codons, 970, 986, 1023, 1024 Storage diseases, 704, 706–707 Storage polysaccharides, 231–232 STRs (short tandem repeats), 73, 1040 Strain, in lysozyme mechanism, 344 Strand-passage mechanism, 843, 845–847 Streptavidin, 618 Streptomyces antibioticus, 950 Streptomyces lividans, 298 Streptomyces mediterranei, 950 Streptomycin, 1020, 1021 Striated muscle, 201–207 thick filaments, 201–205, 204F thin filaments, 201, 205–207, 206F, 210F Stroke, 625, 705, 713 Stroma, 631 Stromal lamellae, 632 Strong acids, 34 Stroud, Robert, 347 Structural bioinformatics, 155–158, 156T Structural genes, 941 Structural genomics, 167 Structural polysaccharides, 230–231 Structure-based drug design, 392 Stubbe, JoAnne, 814 su3 suppressor, 1024 Subcloned DNA, 70 Subdomains, 276 Submitochondrial particles, 627 Substitutional editing, 971–972 Substrates, 323 co-, 326 in competitive inhibition, 374–379 dNTP, 58 leading vs following, 373 lysozyme interactions with, 341F Michaelis–Menten parameters, 368T ribonucleotide reductase, 814 specificity of, 324–326 suicide, 821 urea cycle and availability of, 732–733 Substrate cycles, 452, 506–507, 549F Substrate cycling, 506–507, 507F Substrate-level phosphorylation, 458, 492 Subtilisin, 349F Subunits, 98 See also specific subunits protein, 158–159 separating, 110–113 Subunit IV (cytochrome b6f), 645 Succinate, 586 in citric acid cycle, 374, 559, 560F, 573F, 574 in glyoxylate cycle, 584F in ketone body conversion, 686F Succinate-coenzyme Q oxidoreductase, see Complex II Succinate dehydrogenase, 374, 375, 574, 574F Succinate semialdehyde, 586 Succinate thiokinase, 572–573, 573F Succinyl-CoA, 461 in amino acid degradation, 733F, 738–743, 739F, 742F in citric acid cycle, 560F, 572–573, 573F in heme biosynthesis, 758–762, 759F in ketone body conversion, 686F in oxidation of odd-chain fatty acids, 678F, 679 in oxidation of unsaturated fatty acids, 682–684, 683F Succinyl-CoA synthetase, 572–573, 573F Succinyl-phosphate, in citric acid cycle, 573, 573F Sucralose, 229 Sucrose, 229, 364, 556, 656 Sucrose-phosphate phosphatase, 656 Sucrose-phosphate synthase, 656 Sudden infant death syndrome (SIDS), 675 Südhof, Thomas, 285 Sugars See also specific sugars amino, 226 anomeric forms, 224, 225F conformations, 224, 225 cyclic, 224 deoxy, 226 modification and covalent linking of, 225–227 nucleotide, 552, 552F reducing and nonreducing, 227 Sugar–phosphate backbone, DNA, 840 Suicide substrates, 821 Sulbactam, 238 Sulfa drugs, 740 Sulfanated glycosaminoglycans, 233–234 Sulfanilamide, 740 Sulfatide, 706 Sulfhydryl group, 335F Sulfonamides, 740, 805 Sulston, John, 63 Sumner, James, 322 SUMO (small ubiquitin-related modifier), 1026 Supercoiled DNA, 840–848, 840F, 841F controlled rotation to relax, 844, 845 nicking a strand to relax, 841 progressive unwinding, 842F relaxing negatively supercoiled DNA, 843–844 superhelix topology, 840–841 and topoisomerase, 842–847 during transcription, 944, 944F unwinding DNA circles, 841–842, 842F Supercoiling, 840, 840F Superhelicity, 840 Superhelix topology, 840–841 Superoxide dismutase (SOD), 625–626, 625F Superoxide radical, 624 Supersecondary structures, 151–152, 151F Supply–demand processes, 452 Suppressors, 983, 1024, 1082–1085 Surface labeling, 263 Surfactant, lung, 249, 251 Surroundings, 11 Sutherland, Earl, 424, 526, 542 Suv39h, 1060 SV40 (simian virus 40), 842F, 955 Svedbergs (S), 109, 721 Sweet N Low®, 229 SWI/SNF, 1054 Swiss-PDB Viewer, 157 Swiss roll barrel, 153F Switch regions, 427 sxl gene, 970 SXL protein, 970 Symbiosis, Symmetry: of F1 component, 613–614 of proteins in membranes, 263 of protein subunits, 159, 159F Symmetry model of allosterism, 196, 196F Symport, 309, 309F, 315–316, 316F Synapses, 285, 285F Synaptic cleft, 285 Synaptic vesicles, 285 Synaptobrevin, 285F Synchrotron, 146 Syn conformation, 839, 839F Syncytium, 1089 Synonyms (codon), 986 Syntaxin, 285F Synthase, 693F α-Synuclein, 175 Syphilis, 568 Systematic name, 324 Systems, 11, 18–19 Systems biology, 471–474 Szent-Györgyi, Albert, 143, 203, 561 Szostak, Jack, 902 T, see Thymine T (supercoiled DNA twist), 841, 841F t1/2, see Half-life TAFs (TBP-associated factors), 958–960 TAF1, 1057–1059, 1059F TAF5, 1057 TAF6, 1057 TAF9, 1057 TAF10, 1057 TAF12, 1057 Tagamet (cimetidine), 826 D-Tagatose, 223F Tails, ribosomal proteins, 1000 Tainer, John, 817, 911 D-Talose, 222F Tamiflu (oseltamivir), 375, 375F Tandem mass spectrometry (MS/MS), 117F Tangier disease, 714 Taq polymerase, 71 T arm (tRNA), 988 Tarui’s disease, 530–531 TATA-binding protein (TBP), 957–961, 957F TATA box, 955, 957–958, 958F, 960 Tatum, Edward, 51 Taurine, 665 Tautomers, 47, 47F Taxonomy, Taylor, Susan, 428 Tay-Sachs disease, 253, 706, 707 TBHA2, 288, 289F TBP, see TATA-binding protein TBP-associated factors (TAFs), 958–960 TC10 protein, 439 T cells (T lymphocytes), 212 T cell receptors, 418 TE (palmitoyl thioesterase), 268, 692 Telomerase, 902–905 I-31 I-32 Index Telomeres, 869, 902–904 Temin, Howard, 900 Temperature: and equilibrium constant, 17 and fluidity of lipid bilayers, 261 melting, 851, 851F, 852 and protein stability, 100 transition, 261 Template, DNA, 49, 57 Template switching, 899 Teosinte, 64, 64F TerA site, 895, 896 TerB site, 895, 896 TerC site, 895, 896 TerD site, 895, 896 TerE site, 895, 896 TerF site, 895, 896 TerG site, 895, 896 TerH site, 895, 896 TerI site, 895, 896 TerJ site, 895, 896 Terminal deoxynucleotidyl transferase, 1079 Terminal desaturases, 695 Termination: in chain-terminator technique, 58–59 DNA replication, 895–897 of eukaryotic transcription, 961 of prokaryotic transcription, 946–948 of transcription, 1048–1050 Termolecular reactions, 363 Terpenoids, 256–257 Tertiary structure (proteins), 131, 132F, 145–158 combinations of secondary structures in, 150–154 conservation of, 154–155 determination of, 145–149 polarity and side chain location, 149–151 and structural bioinformatics, 155–158 TERT subunit (telomerase), 903, 903F, 904 Ter–Tus system, 895–897 Testicular feminization, 407 Testosterone, 254, 255F, 406 Tetanus, 286 Tetracycline, 1021 Tetracycline-resistant bacteria, 1021 Tetrahedral intermediates: chymotrypsin, 350, 353–355, 354f serine protease, 351F Tetrahedral symmetry, 159F 5,6,7,8-Tetrahydrobiopterin, 746, 747F Tetrahydrofolate (THF): in amino acid degradation, 738–741, 740F, 741F, 741T in dUMP formation, 818–820 Tetrahydropterotlglutamic acid, 738 Tetrahymena species: ribozyme tertiary structure, 975–976 self-splicing rRNAs, 974–975, 974F telomerase, 902, 903F, 905 Tetrahymena thermophila, 976F, 1057–1058, 1058F Tetraloop, 975 Tetramers, 47 Tetramethyl-p-phenylenediamine, 619 Tetroses, 223 TeTx (tetanus neurotoxin), 286 TFIIA, 958–960 TFIIB, 958–961, 959F TFIIBC, 959 TFIIBN, 959 TFIID, 957, 960, 1059 TFIIE, 959, 960 TFIIF, 959, 961 TFIIH, 959–961 TFIIS, 954 TFIIIA, 864 TFIIIB, 960 TGN (trans Golgi network), 280 β-Thalassemia, 76 Thalidomide, 91, 91F ThDP, see Thiamine pyrophosphate Theobromine, 431 Theophylline, 431 Therapeutic index, 395 Thermodynamics, 11–20 of catabolic vs anabolic pathways, 450 of diffusion, 294–295 of electron transport, 593–594 of fatty acid oxidation, 676 of fermentation, 501, 502 first law of, 11–13 free energy in, 14–18 and homeostasis, 18–20 of membrane transport, 294–295 of metabolism, 449–450 of nonpolar molecules with solvents, 28, 28T second law of, 13 Thermogenesis, 507, 620, 789–790 Thermogenin, 620, 790 Thermophiles, Thermostable proteins, 162 Thermosynechococcus elongatus, 642F, 646, 647F Thermosynechococcus vulcanus, 644, 644F Thermotoga maritima, 977, 977F Thermus aquaticus, 71 DNA polymerase I, 886 DNA polymerase III, 888F EF-Tu, 1012F RNA polymerase, 940, 940F Thermus thermophilus: ATPase, 615 Complex I, 597F, 598 EF-G with GMPPNP, 1018F mRNA in 30S subunit, 1007F ribosomal RNA, 999, 999F ribosomes, 1001F, 1004, 1013, 1013F, 1014F RNA polymerase, 940, 940F RRF, 1023–1024, 1023F, 1024F θ replication, 881 θ structures, 881 THF, see Tetrahydrofolate Thiamine (vitamin B1), 499–501 Thiamine pyrophosphate (TPP; ThDP): in acetyl-CoA synthesis, 564, 565 as cofactor for pyruvate decarboxylate, 499–500 as covalent catalyst, 335 in pentose phosphate pathway, 516F riboswitches for biosynthesis of, 1050–1052 of Saccharomyces uvarum, 499F Thiazolidinediones (TZDs), 795 Thiazolinone, 115F Thiazolium ring, 500 thi box, 1050 Thick filaments, 201–205, 204F Thin filaments, 201, 205–210, 206F, 210F Thioesters, 460–461 Thiogalactoside transacetylase, 941F, 1044 Thiohemiacetal, 490 Thiokinases, 672, 673F Thiolase, 674–676 Thioredoxin, 658, 814–816, 816F Thioredoxin reductase, 816 30-nm fiber, 871, 871F, 872 30S subunit (rRNA), 997, 997T, 999–1002 Thompson, Leonard, 794 Thr, see Threonine Threading, 167 3′ end, nucleic acids, 46 Threonine (Thr): biosynthesis, 752–753, 753F breakdown, 734–736, 734F, 738, 739F discovery, 81 and O-linked oligosaccharides, 240 uncharged polar side chain, 85 Threonine dehydrogenase, 735 D-Threose, 222F Thrombin, 356, 357 Thromboxanes, 258 ThrRS, 994 Thylakoid, 632, 650F Thylakoid membrane, 631–632, 640F, 649 Thymidylate (deoxythymidine monophosphate; dTMP), 818, 819F, 820, 821 Thymidylate synthase, 818, 819F Thymine (T), 43 base pairing, 49F, 849F and Chargaff’s rules, 47 as deoxynucleotide, 44 origin, 817–820 in pyrimidine catabolism, 827F tautomeric forms, 47F Thymine dimer, 905 Thyroid hormones, 1068 Thyroxine, 93–94, 93F Tiglyl-CoA, 742F TIM, see Triose phosphate isomerase TIM barrel, see α/β barrel Time, in rate equations, 363–364 Tissue damage, 726 Tissue factor, 356 Titin, 98, 207, 964 Titration curves, 36–37, 36F, 37F Tjian, Robert, 1058 T loops, 1081 T lymphocytes (T cells), 212 Tm, see Melting temperature, DNA TMs, see Transmembrane proteins Tn3 transposon, 930 TNBS (trinitrobenzenesulfonic acid), 274, 275F TnC, 207 TnI, 207 tnpA gene, 930 TnpA transposon, 930 tnpR gene, 930 TnpR transposon, 930 TnT, 207 α-Tocopherol, 257 Tomato bushy stunt virus, 178 Topoisomerases, 842F and DNA supercoiling, 842–847 inhibitors of, 848 Type I, 842–845, 845F Type IA, 842–844, 843F, 844F Type IB, 842, 844, 845, 845F Type II, 842, 845–848, 846F, 847F Type III, 843–844, 843F Type IV, 897 Topologically linked DNA strands, 841 Topology, of β sheet strands, 139, 140, 140F Torpedo model, 963 Torsion angles, polypeptides, 133, 134, 134F Tosyl-L-lysine chloromethylketone, 346 Tosyl-L-phenylalanine chloromethylketone (TPCK), 346, 347F Totipotent nuclei, 1089 Toxicity, bioavailability and, 393 Toxoplasma gondii, 810, 810F Toxoplasmosis, 810 Toyoshima, Chikashi, 310, 313 TPCK (tosyl-L-phenylalanine chloromethylketone), 346, 347F TPP, see Thiamine pyrophosphate TPP-sensing riboswitch, 1050, 1051F TψC arm (tRNA), 988 tracrRNA, 926 tra gene, 970–971, 970F Trans-acting factors, 1063 Transaldolase, 515–517, 517F Transaminases, 725 Transamination, 551, 725–727 Trans cisternae, 280 Transcobalamins, 680 Trans conformation, 133, 133F Transcortin, 406 Transcripotome, 70 Transcription, 52, 52F, 832, 938–979 in carcinomas, 474F chain elongation, 943–946, 944F eukaryotic, 948–961 of human genome, 1037 inhibitors, 950–951 initiation of, 942–943, 956–961 posttranscriptional control, 1069–1076 posttranscriptional processing, 961–978 prokaryotic, 939–948 promoters, 942–943, 954–956 rate of, 945–946 repressors of, 861–863 RNA polymerases, 939–941, 949–956 termination of, 946–948, 1048–1050 transcription factors, 956–961 Transcriptional activators, 1063–1069 insulators, 1066 JAK-STAT pathway, 1066–1068 Mediator, 1065–1066 for nuclear receptors, 1068–1069 and PIC, 1064–1065 and signal transduction pathways, 1066 Transcriptional coactivators, 1056–1059 Transcriptional initiation complex model, 1059F Index Transcription bubble, 943 Transcription factors, 415 DNA–protein interactions, 864–867 for elongation, 961 eukaryotic, 956–961 Hox genes for, 1094–1095 leucine zippers, 866–867, 866F PIC formation, 957–958, 958F promoters without TATA boxes, 960 TBP, 960–961 and termination of transcription, 961 TFIIA and TFIIB, 958–960 Transcriptome, 53, 471 Transcriptomics, 53, 472–474 Trans fats, 249 Transferrin, 571 Transferrin receptors, 571 Transfer RNA, see tRNA Transformations, 51, 51F, 416 Transformylase, 1006 Transgenes, 74–75 Transgenic organisms, 74–75, 74F Transgenic plants, 75 α(1 → 4) Transglycosylase, 528–529, 529F Trans Golgi network (TGN), 280 Transimination, 727F Transition metal ions, 335–336 Transition mutations, 905 Transition state: defined, 327 enzyme preferential binding in, 338–339, 338F, 350, 352, 352F Transition state analogs, 339, 344, 344F, 375–376 Transition state diagram, 327–330, 328F, 329F Transition state theory, 327, 369 Transition temperature, 261 Transketolase, 515–517, 516F, 652 Translation, 1004–1024 chain elongation, 1011–1022 chain initiation, 1006–1011 chain termination, 1023–1024 control of, 1076 direction of ribosome read, 1005 initiation, 1009F and nucleic acid structure, 832 and O-linked oligosaccharide formation, 553 posttranslational protein processing, 1024–1029 and protein synthesis, 52, 52F, 53F ribosomal activities, 1011–1022 Translocation, 297, 1012, 1017–1021 Translocation systems, 309F Translocons, 279–280 Transmembrane domains, 301F Transmembrane helices, 264–266, 264F, 424–426 Transmembrane proteins (TMs), 276–280 α helices in, 264–266 amphiphilic nature of, 263 β barrels in, 266–267 in endoplasmic reticulum, 277–279 in purple photosynthetic bacteria, 637–638 translocons as, 279–280 Transmembrane ring, of F0, 614–615 Transmissible spongiform encephalopathies (TSEs), 174 Transmission coefficient, 369 Transpeptidation, 1012, 1015–1016 Transport cycle, 307 Transporters, 295 Transport proteins, 293, 305–309, 714 Transport speed, 299 Transposable elements, 929–931 Transposase, 929 Transposition, 64, 929–933 Transposons, 916, 929–931, 930F, 1040–1042 Transverse diffusion, 260, 260F Transversion mutations, 905, 907 TRA protein, 970, 971 Trastuzumab (Herceptin), 216, 420 Treadmilling, 210–211, 211F Trentham, David, 490 Triacylglycerols: biosynthesis of, 696–697, 696F, 700–703 catabolism of, 446F digestion and absorption of, 665–667 function and structure, 248–249, 664–665 in liver, 779 in starvation, 791 transport, 669F Triacylglycerol lipase, 665–666, 698 Tribolium castaneum, 903, 903F Tricarboxylate transport system, 687, 688F TRiC chaperonin, 172 Triclosan, 716 2,5,8-Trienoyl-CoA, 677F 3,5,8-Trienoyl-CoA, 677F Δ2,Δ4,Δ8-Trienoyl-CoA, 677F Trifluoroacetic acid, 114, 116 Trigger factor, 169, 1025–1026, 1025F Triglycerides, see Triacylglycerols Trihexosylceramide, 706 Trimers, 47 Trimethoprim, 821 Trinitrobenzenesulfonic acid (TNBS), 274, 275F Trinucleotide repeats, 1040–1041 Trinucleotide repeat diseases, 1040–1041 Trioses, 223 Triose phosphate isomerase (TIM), 153F, 485, 487–488, 487F Tripeptides, 84 Triple helix, of collagen, 142–144, 142F, 143F Triskelions, 283, 283F Tris(2,3-dibromopropyl)phosphate, 909 tRNA (transfer RNA), 53, 938, 988–996 aminoacyl-tRNA synthetase, 990–994 cloverleaf secondary structure, 984F, 989F codon recognition by, 994–995 EF-Tu ∙ tRNA complex, 1018 identity elements, 992, 992F initiator, 1006–1011 isoaccepting, 992, 995 modified bases, 989, 989F and mRNA, 1002F nonsense suppressor, 1024 posttranscriptional processing, 977–978 proofreading, 993–994 with ribosome and mRNA, 1001F ribosome binding sites, 1001–1002 stacking interaction stabilization, 853, 853F structure, 988–990, 989F, 992–993 tertiary structure, 989, 990, 990F tRNAAla (alanine tRNA), 988 tRNAAsp, 992, 993, 993F tRNAfMet, 1006 tRNAGln, 992, 992F, 993 tRNAi, 1010 tRNAIle, 993F tRNAmMet, 1006 tRNAPhe, 853, 853F, 977, 977F, 990, 990F tRNAPyl, 996 tRNASec, 996 tRNATyr, 978, 978F Trombone model, 892, 892F Tropomodulin, 207 Tropomyosin, 206, 210, 210F α-Tropomyosin, 969, 969F Troponin, 207, 207F Trp, see Tryptophan trpL mRNA, 1049, 1049F trp operon, 941, 1048–1050, 1048F, 1050F trp repressor, 862, 863F Trueblood, Kenneth, 681 Trypsin, 129, 346 and BPTI, 353–354, 353F peptide bond hydrolysis, 372 polypeptide degradation, 114, 724 substrate specificity, 348–349, 348F trypsinogen activation to, 355, 355F, 356 X-ray structure, 346–350, 347F Trypsinogen, 355–357, 355F Tryptophan (Trp): biosynthesis, 755, 755F breakdown, 744, 744F genetic code specification, 986 nonpolar side chain, 84 and trp operon, 1049–1050, 1050F UV absorbance spectra, 102F Tryptophan synthase, 756–757, 756F TSEs (transmissible spongiform encephalopathies), 174 Tsix gene, 1053 T state: glycogen phosphorylase, 389, 389F, 390, 390F hemoglobin, 190–192, 196, 197 I-33 Tsukihara, Tomitake, 306 Tswett, Mikhail, 103 Tth RNAP holoenzyme, 940, 940F Tumor necrosis factor-α, 788 Tumor suppressors, 1082–1085 Turnover number, 368 tus gene, 896 Tus protein, 896, 896F TVGYG (signature sequence), 299 20S proteasome, 721–723 23S rRNA, 973, 997–999 26S proteasome, 721, 721F, 722F 28S rRNA, 973 Twist, supercoiled DNA, 841, 841F [2Fe–2S] clusters, 598 Two-center electron transport, photosynthesis, 639–650 cytochrome b6f, 645–646 plastocyanin, 645–646 PSI-activated electrons, 648–650 PSII and PbRC, 641–643 PSI RC and PSII RC, 646–648 water-splitting reaction, 643–644 Two-dimensional (2D) gel electrophoresis, 108, 108F Two-dimensional (2D) nuclear magnetic resonance spectroscopy, 148 Two-step reactions, 328–329, 328F TxB2, 258F Type diabetes mellitus, 793 Type diabetes mellitus, 793–795 Type I glycogen storage disease, 531 Type I restriction endonucleases, 54 Type II restriction endonucleases, 54–56, 55F Type III restriction endonucleases, 54 Type I topoisomerases, 842–845, 845F Type IA topoisomerases, 842–844, 843F, 844F Type IB topoisomerases, 842, 844, 845, 845F Type II topoisomerases, 842, 845–848, 846F, 847F Type III topoisomerases, 843–844, 843F Type IV topoisomerases, 897 Tyramine, 771 Tyrosine (Tyr): acid-base catalysis by, 332 biosynthesis, 755, 755F breakdown, 745, 746, 747F in neurotransmitter synthesis, 762–763, 763F in phenylalanine breakdown, 471F, 745F uncharged polar side chain, 85 UV absorbance spectra, 102F Tyrosine kinase-associated receptors, 418 Tyrosyl–tRNA, 1020 TyrRS, 994 TZDs (thiazolidinediones), 795 U, see Uracil U, see Energy U1-70K, 967 U1-A, 967 U1-C, 967, 968F U1-snRNA, 966, 967 U2-snRNP, 966, 967 U2-snRNP auxiliary factor (U2AF), 970, 971 U4-snRNP, 966, 967 U5-snRNP, 966, 967 U6-snRNP, 966 Ubiquinone, see Coenzyme Q Ubiquitin, 720–721, 720F Ubiquitin-activating enzyme (E1), 720 Ubiquitin-conjugating enzyme (E2), 720 Ubiquitin isopeptidases, 720 Ubiquitin-protein ligase (E3), 720 UCP1, 620, 790 UCP2, 620 UCP3, 620 UDG (uracil-DNA glycosylase), 911–912, 911F UDP (uridine diphosphate), 510 UDPG (UDP-glucose), 511F, 532 UDP-galactose, 510, 511F UDP-galactose (uridine diphosphate galactose), 552 UDP-galactose-4-epimerase, 510 UDP-glucose (UDPG), 511F, 532 UDP-glucose pyrophosphorylase, 532–533, 533F Ultracentrifugation, 106–108 Ultracentrifuge, 109 Umami, 747 UMP (uridine monophosphate), 809–811, 809F, 827F I-34 Index Uncharged polar side chains, amino acid, 83T, 85, 85F, 150 Uncompetitive enzyme inhibition, 380–381, 380T, 381F, 382F Uncouplers, 620 Uncoupling protein, 620 Underwinding, of DNA circles, 841, 842 Unfavorable processes, 14 Unfolded regions, protein, 164–165 Unimolecular reactions, 362, 363, 363F Uniport, 309, 309F UniProt database, 118T, 119F Units, 12 Unsaturated fatty acids, 247, 247T, 676–678 Untranslated region (UTR), 1040 Unwin, Nigel, 264, 265 Upstream promoter element, 954 Uracil (U), 43 base pairing, 849F and DNA, 911 excision, 911, 912 modified forms of, in tRNA, 989F from oxidative deamination, 906F as primordial base, 986 in pyrimidine catabolism, 827F as ribonucleotide, 44 Uracil-DNA glycosylase (UDG), 911–912, 911F Urate, 824 Urate oxidase, 825 Urea, 319 as chaotropic agent, 162 in urea cycle, 729, 730F, 732 from uric acid, 825F Urea cycle, 728–733, 730F Urease, 322 Ureido group, 546 β Ureidoisobutyrate, 827F β Ureidopropionate, 827F Urey, Harold, Uric acid, 824 degradation of, 825–826 from purine catabolism, 822–825, 822F, 825F and purine ribonucleotide synthesis, 803 in urea cycle, 729 Uridine, 827F, 974 Uridine diphosphate (UDP), 510 Uridine diphosphate galactose (UDP-galactose), 552 Uridine diphosphate glucose (UDP-glucose), 511F, 532 Uridine monophosphate, see UMP Uridine triphosphate, see UTP Uridylylation, 750, 751 Uridylyl-removing enzyme, 751 Uridylyltransferase, 750, 751 Urobilin, 761, 761F Urobilinogen, 761, 761F Urocanate, 737F Uronic acid, 226 Uroporphyrinogen III, 758, 759F Uroporphyrinogen decarboxylase, 759 Uroporphyrinogen synthase, 758 Uroporphyrinogen III synthase, 758 UTP (uridine triphosphate), 533F, 811, 811F UTR (untranslated region), 1040 U4–U6-snRNP, 966 UV absorbance spectra, 102, 102F, 851, 851F UvrABC endonuclease, 912 UvrA protein, 912 UvrB protein, 912 UvrC protein, 912 UvrD (helicase II), 912 V (volt), 12 v (velocity of reaction), 362 vo (initial velocity of reaction), 367, 367F Vacuoles, Valine (Val): biosynthesis, 754–755, 754F breakdown, 742–743 genetic code specification, 985, 987 nonpolar side chain, 84 Valine aminotransferase, 754F Valinomycin, 296–297, 296F ValRS, 994 Vancomycin, 238 Van der Waals distance, 24 Van der Waals forces, 26 Vane, John, 705 Van Leeuwenhoek, Antoni, 203 Van Schaftingen, Emile, 779 Van’t Hoff plot, 17 app VM , 380 Variable arm (tRNA), 989 Variable region, 212–214 Variants (hemoglobin), 197–198, 197T Varshavsky, Alexander, 720 Vassylyev, Dmitry, 940 VAST (computer program), 158 v-ebrB oncogene, 416 Vectorial protons, 609 Vectors, 67, 72 Velocity of reaction (v), 362 Venter, Craig, 62, 63 Very low density lipoproteins (VLDL), 667, 669 Vesicles: clathrin-coated, 282–284, 283F, 670, 671 as first cells, fusion of, 282F, 284–289, 285F, 287F GLUT4 storage, 782 intracellular, 280–289 protein transport by, 280–284 secretory, 281F synaptic, 285 Vestibules, Cl- channel, 304 v-fos viral gene, 416 VH (variable region), 214 Viagra (sildenafil), 432 Vibrio cholerae, 431, 472 Vioxx, 392, 395, 705 Viral fusion protein, 287 Virulence, bacterial, 236 Viruses, adenovirus-2, 964 baculo-, 67 fusion protein use by, 286–289 HIV, 900, 901 influenza, 286, 288F membrane-enveloped, 286 retro-, 900–901, 933 Rous sarcoma, 416 SV40, 842F, 955 tomato bushy stunt, 178 Virus-induced human cancer, 479 Vitamins, 255–257, 443–445, 444T Vitamin A, 75, 257 Vitamin B1 (thiamine), 499–501 Vitamin B2 (riboflavin), 463, 463F Vitamin B3 (pantothenic acid), 461 Vitamin B6 (pyridoxine), 526, 725, 725F Vitamin B12 (cobalamin), 679, 680 Vitamin C, 136, 142 Vitamin D, 255–256 Vitamin D2 (ergocalciferol), 255, 256 Vitamin D3 (cholecalciferol), 255, 256 Vitamin D intoxication, 256 Vitamin E, 257 Vitamin K, 257 V(D)J joining, 1079 V(D)J recombinase, 1079 v-jun viral gene, 416 VL (variable region), 214 Vλ, 1078 VLDL (very low density lipoproteins), 667, 669 Vmax (maximal reaction velocity), 367 from kinetic data, 369–372 Lineweaver-Burk plot for, 370–371, 370F Volt (V), 12 Voltage-gated channels, 300, 301 Voltage gating, in Kv, 301–303 von Euler, Ulf, 258 von Gierke’s disease, 530 von Liebig, Justus, 322 Voorhees, Rebecca, 1028 v-ras oncogene, 416 v-Ras protein, 416 Vκ segment, 1077, 1078 v-src gene, 416 V-type ATPases, 310 W (number of equivalent configurations), 13 w (work), 12, 15 W (writhing number), 841, 841F Waksman, Gabriel, 886 Walker, John, 613 Wall (of Rpb2), 952 Wallin, Ivan, 10 Wang, Andrew, 835 Wang, James, 842 Warburg, Otto, 453, 479, 561, 796 Water, 23–39 activity, 17 buffers, 36–39 chemical properties, 31–39 diffusion, 29–31 hydrocarbon transfer to nonpolar solvents, 28, 28T hydrogen bonds in, 24–25 hydrophilic substances in, 27 hydrophobic effect, 27–29 interface of lipids and, 665–667 ionization, 32–33 nitrogen excretion to conserve, 825 osmosis, 29–31 pH, 33–39 in photosynthesis, 630, 631, 639–641, 643 physical properties, 24–31 polarity of, 24–27 reduction of oxygen to, 607–609 rings of water molecules, 25F structure of, 24F, 25–26 transmembrane movement of, 304–305 Waters of hydration, 27 Water-soluble vitamins, 444–445, 444T Water-splitting enzyme, 643–644 Watson, Herman, 347 Watson, James, 47, 131, 203, 832, 833, 879, 997 Watson–Crick base pairs, 834F, 849, 886–887 Watson–Crick structure, of DNA, 47–50 WD repeat, 711 Weak acids, 34–36 Weak bases, 35–36 Weintraub, Harold, 1053 Weiss, Samuel, 939 Wernicke-Korsakoff syndrome, 500, 501 Western blotting, 107, 859 Wheat germ, 1027F Wieschaus, Eric, 1090 Wigley, Dale, 920 Wild-type sequences, 74 Wiley, Don, 288 Wilkins, Maurice, 833 Williams, Loren, 1004 Wilson, Keith, 1086, 1087 Wiskott-Aldrich syndrome, 76 Withers, Stephen, 344 Wobble hypothesis, 995, 995T Wobble pairs, 995F Woese, Carl, 9, 1004 Wolfenden, Richard, 338, 1016 Work (w), 12, 15 Writhing number, DNA, 841, 841F Wüthrich, Kurt, 147 Wyman, Jeffries, 196 X-ALD (X-linked adrenoleukodystrophy), 76, 684 Xanthine, 806, 822F, 824 Xanthine oxidase (XO), 824–825, 824F Xanthomas, 713 Xanthosine, 822F Xanthosine monophosphate, see XMP X chromosome inactivation, 1053 Xenobiotics, 393 Xenopus borealis, 956 Xenopus laevis, 864 Xeroderma pigmentosum (XP), 913 X-gal, 68 X-inactivation center (XIC), 1053 Xist gene, 1053 X-linked adrenoleukodystrophy (X-ALD), 76, 684 X-linked phosphorlyase kinase deficiency, 531 XMP (xanthosine monophosphate), 806, 806F, 822F XO (xanthine oxidase), 824–825, 824F XP (xeroderma pigmentosum), 913 X-ray crystallography: enzymes, 340, 340F, 344 hemoglobin, 186 protein tertiary structure, 145–147 X-ray free-electron laser, 644 Xrn1, 1070 Xrn2 (Rat1), 963 Index Xu5P, see Xylulose-5-phosphate Xylitol, 226 D-Xylose, 222F D-Xylulose, 223F Xylulose-5-phosphate (Xu5P): in Calvin cycle, 653F, 654 in pentose phosphate pathway, 513F, 514, 515, 516F YO2 (fractional saturation), 183–184, 189–190 Y723F mutant topoisomerase I, 845F YACs (yeast artificial chromosomes), 67, 70 YADH (yeast alcohol dehydrogenase), 501 Yalow, Rosalyn, 404 Yamamoto, Keith, 1069 Yamamoto, Masaki, 644 Yanofsky, Charles, 1049, 1050 Yeast, 498F See also specific species AspRS ∙ tRNAAsp, 993F Complex III, 604F fermentation, 478, 498–499, 499F Mediator complex, 1065–1066, 1065F NHPHA, 1055, 1055F, 1056 Phe–tRNAPhe, 1012F phosphoglycerate kinase, 491F phosphoglycerate mutase, 492F preinititiation complex, 960F RNA polymerase II (RNAP II), 949, 949F, 950 topoisomerase II, 846F tRNAPhe, 853F, 990, 990F tRNATyr, 978, 978F 26S proteasome, 722F Yeast alcohol dehydrogenase (YADH), 501 Yeast artificial chromosomes (YACs), 67, 70 Yeast hexokinase, 482F Yersinia pestis, 422 -yl (suffix), 87 Ylid, 500 Yonath, Ada, 999, 1008 YopH, 422 Yoshikawa, Shinya, 607 Young, William, 478 Yusupov, Marat, 1003 I-35 Zalcitabine (2′,3′-dideoxycytidine, ddC), 376 Zα, 835, 837F Zamecnik, Paul, 996 Zamore, Phillip, 1072 Z disk, 201 Z-DNA, 834–837, 835T, 836F–837F, 839 Zellweger syndrome, 684 Zeroth order reactions, 364 Zidovudine (3′-Azido-3′-deoxythymidine, AZT), 376 Zif268, zinc finger motif, 161F, 864, 864F Zinc fingers, 161–162, 161F Cys2–His2, 864–866 Cys6, 865 DNA-binding structures, 865F in DNA-binding structures, 864–866, 864F Zn2+ ion, 326, 336, 336F Zocor, 712F Zovir (acyclovir), 826 Z-scheme, 641, 641F Zwitterions, 84 Zymase, 478 Zymogens, 355–357 APPLICATIONS INDEX Diet & Nutrition artificial sweeteners 229 essential amino acids 752 essential fatty acids 695 fructose 509 lactose intolerance 228 pellagra 444 riboflavin 463 scurvy 142 starvation 790 thiamine deficiency 500 threonine 81 trans fats 249 vitamin B12 deficiency 680 vitamin D disorders 256 Drugs & Toxins adrenergic receptor inhibitors 406 anabolic steroids 407 antibiotics and protein synthesis 1020 antibiotics and transcription 950 antifolates 821 arsenic poisoning 568 aspirin 705 bacitracin 555 cardiac glycosides 312 COX-2 inhibitors 705 diabetes drugs 795 drug design 392 drug resistance 314 drug–drug interactions 395 enantiomeric drugs 91 fatty acid synthase inhibitors 693 heparin 234 HIV enzyme inhibitors 376 influenza drugs 375 lead poisoning 758 malaria drugs 391 methanol poisoning 378 nerve poisons 346 oral rehydration therapy 316 penicillin and vancomycin 238 purine derivatives 826 sulfa drugs 740 tetanus and botulinum toxins 286 topoisomerase inhibitors 848 viagra 432 Evolution & Comparative Biochemistry aerobic metabolism 558 α/β barrel enzymes 488 anaerobic metabolism 443 bacterial electron transport 612 citric acid cycle evolution 582 cytochrome c evolution 120 domains of life endosymbiosis 10 fatty acid synthase evolution 689 gene duplication 124 genetic code evolution 986 I-36 globin evolution 124 histone conservation 868 HIV drug resistance 377 homeotic genes 1093 human evolution 66 human phylogenetic tree 1042 mutation 905 natural selection 10 nitrogen disposal strategies 825 oxygen-transport proteins 185 parasite nucleotide metabolism 810 photosystem evolution 641, 648 prebiotic evolution protein structure conservation 154 ribosome structure conservation 1004 RNA world 854 serine protease evolution 349 shared genes 1036 sickle-cell anemia and malaria 199 thioester chemistry 460 transposition 931 uracil in DNA 911 vitamin synthesis 445 Health & Disease ABO blood groups 241 acidosis and alkalosis 38 acute pancreatitis 355 Addison’s disease 255 adrenoleukodystrophy 684 aging and telomerase 905 alcaptonuria 746 Angelman syndrome 1063 antibody diversity 1076 atherosclerosis 713 autoimmune diseases 217 blood buffering 38 blood coagulation 356 breast cancer 925 brown adipose tissue 621 bubonic plague 422 cancer 416, 796, 1082 carcinogenesis 907 cholera and pertussis 431 Cockayne syndrome 913 collagen diseases 143 Cushing’s disease 255 cystic fibrosis 315 diabetes 792 emphysema 354 erythrocyte enzyme deficiencies 494 Galactosemia 511 Gaucher’s disease 707 genetic diseases 65 glucose-6-phosphate dehydrogenase deficiency 518 glycogen storage diseases 530 glyoxylate cycle in pathogens 585 gout 825 growth disorders 407 heart attack and stroke 625 hemoglobin variants 197 hereditary spherocytosis 272 high-altitude adaptation 195 homocysteine as disease marker 740 human splice site variants 969 hyperammonemia 728 hypercholesterolemia 713 I-cell disease 284 jaundice 762 leptin and obesity 789 Lesch–Nyhan syndrome 808 leukemia 420 lipid storage diseases 706 lipoproteins 667 lung surfactant 251 maple syrup urine disease 742 metabolic syndrome 796 microbiome 777 muscle glucose metabolism 502 muscular dystrophy 207 neurodegenerative diseases 624 obesity 792 oncogenes and cancer 416 orotic aciduria 812 pernicious anemia 680 phenylketonuria 746 porphyria 760 Prader–Willi syndrome 1063 protein misfolding diseases 173 retinoblastoma 1085 severe combined immunodeficiency 823 spina bifida and anencephaly 740 sudden infant death syndrome 675 Tangier disease 714 Tay–Sachs disease 706 thermogenesis 507 toxoplasmosis 810 trinucleotide repeat diseases 1040 xeroderma pigmentosum 913 Zellweger syndrome 684 Laboratory & Clinical Tools clinical trials 393 CRISPR-Cas system 927 DNA fingerprinting 73 expanding the genetic code 996 gastric bypass surgery 796 gene therapy 75 green fluorescent protein 93 kidney dialysis 31 monoclonal antibodies 216 organ transplants 423 polyketide synthesis 694 protein design 167 protein sequencing 112 radioimmunoassay 404 receptor–ligand binding 410 recombinant DNA technology, ethical aspects 75 transaminase assays 726 Some Common Biochemical Abbreviations A aaRS ACAT ACP ADA ADP AIDS ALA AMP ATCase ATP BChl bp BPG BPheo BPTI C CaM CAM cAMP CAP CDK cDNA CDP CE Chl CM CMP CoA or CoASH CoQ COX CPS CTP D d DAG DCCD dd ddNTP DEAE DHAP DHF DHFR DNA DNP dNTP E4P EF ELISA EM emf ER ESI ETF F1P adenine aminoacyl–tRNA synthetase acyl-CoA:cholesterol acyltransferase acyl-carrier protein adenosine deaminase adenosine diphosphate acquired immunodeficiency syndrome δ-aminolevulinic acid adenosine monophosphate aspartate transcarbamoylase adenosine triphosphate bacteriochlorophyll base pair D-2,3-bisphosphoglycerate bacteriopheophytin bovine pancreatic trypsin inhibitor cytosine calmodulin crassulacean acid metabolism 3',5'-cyclic AMP catabolite gene activator protein cyclin-dependent protein kinase complementary DNA cytidine diphosphate capillary electrophoresis chlorophyll carboxymethyl cytidine monophosphate coenzyme A coenzyme Q (ubiquinone) cyclooxygenase carbamoyl phosphate synthetase cytidine triphosphate dalton deoxy 1,2-diacylglycerol dicyclohexylcarbodiimide dideoxy 2′,3′-dideoxynucleoside triphosphate diethylaminoethyl dihydroxyacetone phosphate dihydrofolate dihydrofolate reductase deoxyribonucleic acid 2,4-dinitrophenol 2′-deoxynucleoside triphosphate erythrose-4-phosphate elongation factor enzyme-linked immunosorbent assay electron microscopy electromotive force endoplasmic reticulum electrospray ionization electron-transfer flavoprotein fructose-1-phosphate F2,6P F6P FAD FADH∙ FADH2 FBP FBPase Fd FH fMet FMN G G1P G6P G6PD GABA Gal GalNAc GAP GAPDH GDH GDP Glc GlcNAc GMP GPI GSH GSSH GTF GTP Hb HDL HIV HMG-CoA hnRNA HPLC Hsp HTH Hyl Hyp IDL IF IgG IMP IP3 IPTG IR IS ISP kb kD KM LDH LDL LHC Man fructose-2,6-bisphosphate fructose-6-phosphate flavin adenine dinucleotide, oxidized form flavin adenine dinucleotide, radical form flavin adenine dinucleotide, reduced form fructose-1,6-bisphosphate fructose-1,6-bisphosphatase ferredoxin familial hypercholesterolemia N-formylmethionine flavin mononucleotide guanine glucose-1-phosphate glucose-6-phosphate glucose-6-phosphate dehydrogenase γ-aminobutyric acid galactose N-acetylgalactosamine glyceraldehyde-3-phosphate glyceraldehyde-3-phosphate dehydrogenase glutamate dehydrogenase guanosine diphosphate glucose N-acetylglucosamine guanosine monophosphate glycosylphosphatidylinositol glutathione glutathione disulfide general transcription factor guanosine triphosphate hemoglobin high density lipoprotein human immunodeficiency virus β-hydroxy-β-methylglutaryl-CoA heterogeneous nuclear RNA high performance liquid chromatography heat shock protein helix–turn–helix 5-hydroxylysine 4-hydroxyproline intermediate density lipoprotein initiation factor immunoglobulin G inosine monophosphate inositol-1,4,5-trisphosphate isopropylthiogalactoside infrared insertion sequence iron–sulfur protein kilobase pair kilodalton Michaelis constant lactate dehydrogenase low density lipoprotein light-harvesting complex mannose (table continued on following page) ... NH3, H2S, or even Fe2+: NH3 + O2 → HNO3 + H2O H2S + O2 → H2SO4 FeCO3 + O2 + H2O → Fe(OH) + CO2 Photoautotrophs so via photosynthesis, a process in which light energy powers the transfer of electrons... of a metabolic fuel such as glucose C6H12O6 + O2 → CO2 + H2O releases considerable energy (ΔG°′ = 28 50 kJ · mol−1) The complete oxidation of palmitate, a typical fatty acid, C16H32O2 + 23 O2... Half-Life Type of Radiationa 12. 31 years β 14 5715 years β 18 110 minutes β+ 22 2. 60 years β +, γ 32 14 .28 days β 35 87 .2 days β 45 1 62. 7 days β 60 5 .27 1 years β, γ 59.4 days γ 8. 02 days β, γ H
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Xem thêm: Ebook Fundamentals of biochemistry (5/E): Part 2, Ebook Fundamentals of biochemistry (5/E): Part 2, C. Metabolic Pathways Consist of Series of Enzymatic Reactions, E. Metabolic Flux Must Be Controlled, C. Some Other Phosphorylated Compounds Have High Phosphoryl Group-Transfer Potentials, C. Spontaneity Can Be Determined by Measuring Reduction Potential Differences, C. Systems Biology Has Entered the Study of Metabolism, E. Triose Phosphate Isomerase Interconverts Dihydroxyacetone Phosphate and Glyceraldehyde-3-Phosphate, J. Pyruvate Kinase Generates the Second ATP, B. Alcoholic Fermentation Converts Pyruvate to Ethanol and CO2, A. Phosphofructokinase Is the Major Flux-Controlling Enzyme of Glycolysis in Muscle, C. Stage 3 Involves Carbon–Carbon Bond Cleavage and Formation, D. The Pentose Phosphate Pathway Must Be Regulated, A. Glycogen Phosphorylase Degrades Glycogen to Glucose-1-Phosphate, C. Phosphoglucomutase Interconverts Glucose-1-Phosphate and Glucose-6-Phosphate, B. Glycogen Phosphorylase and Glycogen Synthase Undergo Control by Covalent Modification, C. Glycogen Metabolism Is Subject to Hormonal Control, A. Pyruvate Is Converted to Phosphoenolpyruvate in Two Steps, C. Gluconeogenesis and Glycolysis Are Independently Regulated, B. The Pyruvate Dehydrogenase Complex Catalyzes Five Reactions, B. Three Enzymes Control the Rate of the Citric Acid Cycle, C. The Glyoxylate Cycle Shares Some Steps with the Citric Acid Cycle, B. Electron Carriers Operate in Sequence, C. Complex I Accepts Electrons from NADH, E. Complex III Translocates Protons via the Q Cycle, F. Complex IV Reduces Oxygen to Water, A. The Chemiosmotic Theory Links Electron Transport to ATP Synthesis, B. ATP Synthase Is Driven by the Flow of Protons, D. Oxidative Phosphorylation Can Be Uncoupled from Electron Transport, B. Aerobic Metabolism Has Some Disadvantages, B. Pigment Molecules Absorb Light, C. Two-Center Electron Transport Is a Linear Pathway That Produces O2 and NADPH, A. The Calvin Cycle Fixes CO2, D. Photorespiration Competes with Photosynthesis, B. Lipids Are Transported as Lipoproteins, E. Oxidation of Odd-Chain Fatty Acids Yields Propionyl-CoA, F. Peroxisomal β Oxidation Differs from Mitochondrial β Oxidation, C. Fatty Acid Synthase Catalyzes Seven Reactions, E. Fatty Acids Are Esterified to Form Triacylglycerols, A. Glycerophospholipids Are Built from Intermediates of Triacylglycerol Synthesis, C. C20 Fatty Acids Are the Precursors of Prostaglandins, A. Cholesterol Is Synthesized from Acetyl-CoA, B. HMG-CoA Reductase Controls the Rate of Cholesterol Synthesis, C. Abnormal Cholesterol Transport Leads to Atherosclerosis, C. The Proteasome Unfolds and Hydrolyzes Ubiquitinated Polypeptides, A. Transaminases Use PLP to Transfer Amino Groups, A. Five Enzymes Carry Out the Urea Cycle, D. Methionine, Threonine, Isoleucine, and Valine Are Degraded to Succinyl-CoA, G. Phenylalanine and Tyrosine Are Degraded to Fumarate and Acetoacetate, A. Nonessential Amino Acids Are Synthesized from Common Metabolites, B. Plants and Microorganisms Synthesize the Essential Amino Acids, A. Heme Is Synthesized from Glycine and Succinyl-CoA, A. Nitrogenase Reduces N2 to NH3, B. Fixed Nitrogen Is Assimilated into Biological Molecules, B. Glucagon and Catecholamines Counter the Effects of Insulin, B. Diabetes Mellitus Is Characterized by High Blood Glucose Levels, C. Obesity Is Usually Caused by Excessive Food Intake, A. Purine Synthesis Yields Inosine Monophosphate, A. Ribonucleotide Reductase Converts Ribonucleotides to Deoxyribonucleotides, B. dUMP Is Methylated to Form Thymine, A. Purine Catabolism Yields Uric Acid, C. Pyrimidines Are Broken Down to Malonyl-CoA and Methylmalonyl-CoA, A. DNA Can Adopt Different Conformations, D. Topoisomerases Alter DNA Supercoiling, C. RNA Structures Are Highly Variable, B. Electrophoresis Separates Nucleic Acids by Size, B. Prokaryotic Repressors Often Include a DNA-Binding Helix, C. Eukaryotic Transcription Factors May Include Zinc Fingers or Leucine Zippers, B. Chromatin Forms Higher-Order Structures, DNA Replication, Repair, and Recombination, A. DNA Polymerases Add the Correctly Paired Nucleotides, C. The Leading and Lagging Strands Are Synthesized Simultaneously, C. Telomerase Extends Chromosome Ends, A. Homologous Recombination Involves Several Protein Complexes, B. DNA Can Be Repaired by Recombination, C. CRISPR–Cas9, a System for Editing and Regulating Genomes, D. Transposition Rearranges Segments of DNA, A. RNA Polymerase Resembles Other Polymerases, C. The RNA Chain Grows from the 5' to 3' End, D. Transcription Terminates at Specific Sites, A. Eukaryotes Have Several RNA Polymerases, C. Transcription Factors Are Required to Initiate Transcription, B. Splicing Removes Introns from Eukaryotic Genes, C. Ribosomal RNA Precursors May Be Cleaved, Modified, and Spliced, D. Transfer RNAs Are Processed by Nucleotide Removal, Addition, and Modification, B. Aminoacyl–tRNA Synthetases Attach Amino Acids to tRNAs, C. Most tRNAs Recognize More than One Codon, A. The Prokaryotic Ribosome Consists of Two Subunits, B. The Eukaryotic Ribosome Contains a Buried Prokaryotic Ribosome, A. Chain Initiation Requires an Initiator tRNA and Initiation Factors, B. The Ribosome Decodes the mRNA, Catalyzes Peptide Bond Formation, Then Moves to the Next Codon, B. Newly Synthesized Proteins May Be Covalently Modified, A. Gene Number Varies among Organisms, C. Eukaryotic Genomes Contain Repetitive DNA Sequences, A. The lac Operon Is Controlled by a Repressor, A. Chromatin Structure Influences Gene Expression, B. Eukaryotes Contain Multiple Transcriptional Activators, D. Antibody Diversity Results from Somatic Recombination and Hypermutation, B. Tumor Suppressors Prevent Cancer, C. Apoptosis Is an Orderly Process, D. Development Has a Molecular Basis

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