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Part 2 book “MCAT biochemistry review 2019-2020” has contents: RNA and the genetic code, biological membranes, carbohydrate metabolism I - glycolysis, glycogen, gluconeogenesis, and the pentose phosphate pathway, carbohydrate metabolism II - aerobic respiration, lipid and amino acid metabolism, bioenergetics and regulation of metabolism.
In This Chapter 7.1 The Genetic Code Types of RNA Codons Mutations 7.2 Transcription Mechanism of Transcription Posttranscriptional Processing 7.3 Translation The Ribosome Mechanism of Translation Posttranslational Processing 7.4 Control of Gene Expression in Prokaryotes Operon Structure Inducible Systems Repressible Systems 7.5 Control of Gene Expression in Eukaryotes Transcription Factors Gene Amplification Regulation of Chromatin Structure Concept Summary Chapter Profile The content in this chapter should be relevant to about 15% of all questions about biochemistry on the MCAT This chapter covers material from the following AAMC content categories: 1B: Transmission of genetic information from the gene to the protein 5D: Structure, function, and reactivity of biologically-relevant molecules Introduction Hepatitis C virus (HCV) continues to be a major cause of cirrhosis and liver failure in the United States Usually associated with intravenous drug use, hepatitis C causes ongoing damage and inflammation in the liver, leading to the formation of scar tissue that replaces the normal cells of the organ Over time, this buildup of scar tissue makes the liver unable to keep up with the metabolic demands of the body, and liver failure ensues To fight this virus, infected hepatocytes release interferon, a peptide signal that—as the name suggests—interferes with viral replication Because viruses must hijack the host cell’s machinery to replicate, one way the body can limit the spread of the virus is by shutting off the processes of transcription and translation Interferon not only curtails these processes in virally infected cells, but also induces the production of RNase L, which cleaves RNA in cells to further reduce the ability of the virus to replicate Coupled with other immune defenses, interferon thus serves as an efficient mechanism to protect the body from viral pathogens Even in normal, healthy cells, the first step in expressing genetic information is transcription of the information in the base sequence of a double-stranded DNA molecule to form a single-stranded molecule of RNA The second step is translating that nucleotide sequence into a protein Not every cell, though, expresses every gene product, and control of gene expression leads to the differentiation of the totipotent zygote into all of the tissues of the body In this chapter, we will discuss the process through which proteins are produced along with the controls that modulate each step of the path 7.1 The Genetic Code LEARNING GOALS After Chapter 7.1, you will be able to: Differentiate between three different types of RNA: mRNA, tRNA, and rRNA Transcribe a DNA sequence like "GAATTCG" into its mRNA conjugate Define the concepts of wobble and degeneracy Identify the translation outcomes of key codons, including AUG, UAG, UAA, and UGA Predict the likely impact of different mutation types on the resulting peptide An organism must be able to store and preserve its genetic information, pass that information along to future generations, and express that information as it carries out all the processes of life We know that DNA and RNA share the same language: they both code using nitrogenous bases Proteins, however, are composed of amino acids, which constitute a different language altogether Therefore, we use the genetic code to translate this genetic information into proteins While nucleotides play a crucial role in maintaining our genetic identity from generation to generation, it is the proteins they encode that help organisms develop and perform the necessary functions of life The major steps involved in the transfer of genetic information are illustrated in the central dogma of molecular biology, as shown in Figure 7.1 Classically, a gene is a unit of DNA that encodes a specific protein or RNA molecule, and through transcription and translation, that gene can be expressed Although this sequence is now complicated by our increased knowledge of the ways in which genes and nucleic acids may be expressed, it is still useful as a general working definition of the processes of DNA replication, transcription, and translation We have already discussed DNA synthesis, but will continue learning more about gene expression in the rest of this chapter Figure 7.1 The Central Dogma of Molecular Biology The relationship between the sequence found in double-stranded DNA, single-stranded RNA, and protein is illustrated in Figure 7.2 for a prototypical gene Messenger RNA is synthesized in the 5′ → 3′ direction and is complementary and antiparallel to the DNA template strand The ribosome translates the mRNA in the 5′ → 3′ direction, as it synthesizes the protein from the amino terminus (N-terminus) to the carboxy terminus (C-terminus) Figure 7.2 Flow of Genetic Information from DNA to Protein TYPES OF RNA There are three main types of RNA found in cells: mRNA, tRNA, and rRNA Each of the main types is described below, but regulatory and specialized forms of RNA are also described later in the chapter Messenger RNA (mRNA) Messenger RNA (mRNA) carries the information specifying the amino acid sequence of the protein to the ribosome mRNA is transcribed from template DNA strands by RNA polymerase enzymes in the nucleus of cells Then, mRNA may undergo a host of posttranscriptional modifications prior to its release from the nucleus mRNA is the only type of RNA that contains information that is translated into protein; to do so, it is read in three-nucleotide segments termed codons In eukaryotes, mRNA is monocistronic, meaning that each mRNA molecule translates into only one protein product Thus, in eukaryotes, the cell has a different mRNA molecule for each of the thousands of different proteins made by that cell In prokaryotes, mRNA may be polycistronic, and starting the process of translation at different locations in the mRNA can result in different proteins The process of creating mature mRNA will be discussed in the next section of this chapter KEY CONCEPT mRNA is the messenger of genetic information DNA codes for proteins but cannot perform any of the important enzymatic reactions that proteins are responsible for in cells mRNA takes the information from the DNA to the ribosomes, where creation of the primary protein structure occurs Transfer RNA (tRNA) Figure 7.3 The Structure of tRNA acid prosthetic groups are referred to as lipoproteins, glycoproteins, and nuceloproteins, respectively Protein–A molecule made up of at least one chain of amino acids joined by peptide bonds Proteinogenic—The ability of certain (20) amino acids to be integrated into proteins Proton-motive force—The proton concentration gradient across the inner mitochondrial membrane that is created in the electron transport chain and used in oxidative phosphorylation Purine–Nitrogen-containing base found in nucleotides possessing a two ring structure The purines are adenine and guanine Pyranose—A six-membered ring sugar Pyrimidine–Nitrogen containing base found in nucleotides possessing a one ring structure The three pyrimidines are cytosine, thymine, and uracil Pyruvate—An important metabolic intermediate that can feed into the citric acid cycle, fermentation, or gluconeogenesis Q cycle—The shuttling of electrons between ubiquinol and ubiquinone in the inner mitochondrial membrane as a part of Complex III’s function Quaternary structure—The interaction between different subunits of a multi-subunit protein; stabilized by R group interactions Reaction coupling—The tendency of unfavorable biological reactions to occur concurrently with favorable reactions, often catalyzed by a single enzyme Reading frame–In translation, the three nucleotides that make up a codon Recombinant DNA–DNA that has been formed by combining genetic material from multiple sources in a laboratory Reducing sugar—A sugar that can reduce other compounds and can be detected by Tollens' or Benedict’s reagent Regulator gene–In an operon, the gene that codes for the repressor protein Release factor—The protein that binds to the stop codon during termination of translation Renaturation—The regaining of the correct secondary, tertiary, and quaternary structure after denaturation of a protein Replisome–Set of specialized proteins that assist DNA polymerase during replication Repressible system—An operon that requires a repressor to bind to a corepressor before binding to the operator site to stop transcription of the relevant gene Repressor—For enzymes, an inhibitor of enzyme action; for operons, a species that binds to the operator region to stop transcription of the relevant gene Respiratory control—The coordinated regulation of the different aerobic metabolic processes Respiratory quotient—A numerical representation that can be used to determine the most prevalent type of biomolecule being used in metabolism; the ratio of carbon dioxide produced to oxygen consumed Respirometry—A method of measuring metabolism through the consumption of oxygen Resting membrane potential—The electrical potential that results from the unequal distribution of charge around the cell membrane; resting membrane potential characterizes a cell that has not been stimulated Restriction enzyme–Enzymes that recognize palindromic double-stranded DNA sequences and cut through the backbone of the double helix at those locations Ribonucleic acid (RNA)—A nucleic acid found in both the nucleus and cytoplasm and most closely linked with transcription and translation, as well as some gene regulation Ribosomal RNA (rRNA)—The structural and enzymatic RNA found in ribosomes that takes part in translation Ribosome–Organelle composed of RNA and protein; it translates mRNA during protein synthesis Ribozyme—An RNA molecule with enzymatic activity Saponification—The reaction between a fatty acid and a strong base, resulting in a negatively charged fatty acid anion bound to a metal ion; creates soap Saturation—The presence or absence of double bonds in a fatty acid; saturated fatty acids have only single bonds, whereas unsaturated fatty acids have at least one double bond Secondary structure—The local structure of neighboring amino acids; most common areα-helices and β-pleated sheets Sequencing—Determining the order of amino acids in a polypeptide, or of nucleotides in a nucleic acid Shine–Dalgarno sequence—The site of initiation of translation in prokaryotes Shuttle mechanism—A method of functionally transferring a compound across a membrane without the actual molecule crossing; common examples are the glycerol 3-phosphate shuttle and malate–aspartate shuttle Sialic acid—The common name of N-acetylneuraminic acid (NANA), which is the terminal portion of the head group in a ganglioside Side chain—The variable component of an amino acid that gives the amino acid its identity and chemical properties; also called an R group Silent mutation—A mutation in the wobble position of a codon or noncoding DNA that leads to no change in the protein produced during translation Simple diffusion—The movement of solute molecules through the cell membrane down their concentration gradients without a transport protein; used for small, nonpolar, lipophilic molecules and water Single-stranded DNA-binding protein–Proteins that bind to unraveled DNA strands to prevent reassociation of DNA or degradation of DNA during replication events Small nuclear ribonucleoproteins (snRNPs)—The protein portion of the spliceosome complex Small nuclear RNA (snRNA)—The RNA portion of the spliceosome complex Sodium–potassium pump—An ATPase that exchanges three sodium cations for two potassium cations; responsible for maintaining cell volume and the resting membrane potential Solvation layer—The layer of solvent particles that interacts directly with the surface of a dissolved species Sphingolipid—A lipid containing a sphingosine or sphingoid backbone, bonded to fatty acid tails; include ceramide, sphingomyelins, glycosphingolipids, and gangliosides Sphingomyelin—A sphingophospholipid containing a sphingosine backbone and a phosphate head group Spliceosome—The apparatus used for splicing out introns and bringing exons together during mRNA processing Starch—A branched polymer of glucose used for energy storage in plants; common examples are amylose and amylopectin Start codon—The first codon in an mRNA molecule that codes for an amino acid (AUG for methionine or N-formylmethionine) Stereoisomers—Compounds that have the same chemical formula and backbone, differing only in their spatial orientation; also called optical isomers Steroid—A derivative of cholesterol Stop codon—The last codon of translation (UAA, UGA, or UAG); release factor binds here, terminating translation Structural gene–Within an operon, the region that codes for the protein of interest Structural proteins—Proteins that are involved in the cytoskeleton and extracellular matrix; they are generally fibrous in nature and include collagen, elastin, keratin, actin, and tubulin Substrate—The molecule upon which an enzyme acts Substrate-level phosphorylation—The transfer of a phosphate group from a high-energy compound to ATP or another compound; occurs in glycolysis Sucrose—A disaccharide composed of glucose and fructose Supercoiling–Wrapping of DNA on itself during replication, characterized by torsional stress and potential for strand breakage Surfactant—A compound that lowers the surface tension between two solutions, acting as a detergent or emulsifier TATA box—The site of binding for RNA polymerase II during transcription; named for its high concentration of thymine and adenine bases Tautomerization—The rearrangement of bonds within a compound, usually by moving a hydrogen and forming a double bond Telomere–Repeating unit at the end of DNA that protects against the loss of information with repeated DNA replication Template strand—The strand of DNA that is transcribed to form mRNA; also called the antisense strand Termination—The end of translation, in which the ribosome finds a stop codon and release factor binds it, allowing the peptide to be freed from the ribosome Terpene—A class of lipids built from isoprene moieties; have carbon groups in multiples of five Terpenoid—A terpene derivative that has undergone oxygenation or rearrangement of the carbon skeleton Tertiary structure—The three-dimensional shape of a polypeptide, stabilized by numerous interactions between R groups Thyroid hormones—The primary permissive metabolic hormones involved in the regulation of the basal metabolic rate Tight junctions—Cell–cell junctions that prevent the paracellular transport of materials; tight junctions form a collar around cells and link cells within a single layer Titration—A laboratory technique in which a solution of unknown concentration is mixed with a solution of known concentration to determine the unknown concentration Transcellular transport—The transport of materials through the cell; requires interaction with the cytoplasm and may require transport proteins Transcription—The production of an mRNA molecule from a strand of DNA Transcription factors—Proteins that help RNA polymerase II locate and bind to the promoter region of DNA Transfer RNA (tRNA)—A folded strand of RNA that contains a threenucleotide anticodon that pairs with an appropriate mRNA codon during translation and is charged with the corresponding amino acid Transferase—An enzyme that catalyzes the transfer of a functional group Translation—The production of a protein from an mRNA molecule Triacylglycerol—A glycerol molecule esterified to three fatty acid molecules; the most common form of fat storage within the body Uncompetitive inhibition—A decrease in enzyme activity that results from the interaction with an inhibitor at the allosteric site; uncompetitive inhibitors bind only to the substrate-bound enzyme and cannot be overcome by addition of substrate UV spectroscopy—A method of determining the concentration of protein in an isolate by comparison against a protein standard; relies on the presence of aromatic amino acids It can also be used with nucleic acids and other compounds van’t Hoff factor–The number of particles obtained from a molecule when dissociated in solution Vitamin—An organic essential coenzyme that assists an enzyme in carrying out its action vmax–Maximum velocity for a given quantity of enzyme vmax occurs when the enzyme is fully saturated Watson-Crick model–This model proposed the structure of DNA as a double stranded helix Wax—A high-melting point lipid composed of a very long chain alcohol and a very long chain fatty acid Wobble—The third nucleotide of a codon that often plays no role in specifying an amino acid; an evolutionary development designed to protect against mutations X-ray crystallography—A method of determining molecular structure using apparent bond angles and diffraction and refraction of X-rays Zwitterion—A molecule that contains charges, but is neutral overall Most often used to describe amino acids Zymogen—An enzyme that is secreted in an inactive form and must be activated by cleavage; common examples are digestive enzymes Art Credits Chapter 1 Cover—Image credited to Yikrazuul From Wikimedia Commons Figure 1.12—Image credited to George V Kelvin From “The Protein Folding Problem” by Frederic M Richards Copyright © 1991 by Scientific American, Inc All rights reserved Figure 1.13—Image credited to George V Kelvin From “The Protein Folding Problem” by Frederic M Richards Copyright © 1991 by Scientific American, Inc All rights reserved Figure 1.15a—Image credited to ibreakstock From Shutterstock Figure 2.2—Image credited to Michael Goodman From “Drugs by Design” by Charles E Bugg, William M Carson, and John A Montgomery Copyright © 1993 by Scientific American, Inc All rights reserved Chapter 3 Cover—Image credited to Heiti Paves From Shutterstock Figure 3.3—Image credited to Ian Worpole From “How the Immune System Recognizes Invaders” by Charles A Janeway Jr Copyright © 1993 by Scientific American, Inc All rights reserved Figure 3.6—Image credited to Daniels and Daniels From “The Amateur Scientist: Sorting Molecules with Electricity” by Shawn Carlson Copyright © 1998 by Scientific American, Inc All rights reserved Figure 3.7—Image credited to ggw From Shutterstock Figure 3.9—Image credited to User: Dcrjsr From Wikimedia Commons Copyright © 1971 Used under license: CC-BY-3.0 Chapter 4 Cover—Image credited to Sea Wave From Shutterstock Chapter 5 Cover—Image credited to Captain Yeo From Shutterstock Figure 5.4—Image credited to User: Alex Hindemith From Wikimedia Commons Chapter 6 Cover—Image credited to: anyaivanova From Shutterstock Figure 6.16—Image credited to Madeline Price Ball From Wikimedia Commons Copyright © 2011 Chapter 7 Cover—Image credited to: Mopic From Shutterstock Figure 7.5—Image credited to Lucy Reading-Ikkanda From “Evolution Encoded” by Stephen J Freeland and Laurence D Hurst Copyright © 2004 by Scientific American, Inc All rights reserved Figure 7.15—Image credited to Tami Tolpa From “The Power of Riboswitches” by Jeffrey E Barrick and Ronald R Breaker Copyright © 2007 by Scientific American, Inc All rights reserved Chapter 8 Cover—Image credited to somersault1824 From Shutterstock Figure 8.7—Image credited to Holly Fischer From Wikimedia Commons Copyright © 2013 Used under license: CC-BY-3.0 Image in Concept Check 8.2—Image credited to ellepigrafica From Shutterstock Chapter 9 Cover—Image credited to Christian Bertrand From Shutterstock Chapter 10 Cover—Image credited to RAJ CREATIONZS From Shutterstock Figure 10.12—Image credited to Dana Burns Pizer and Tomo Narashima From “Caloric Restriction and Aging” by Richard Weindruch Copyright © 1996 by Scientific American, Inc All rights reserved Figure 10.16—Image credited to Tomo Narashima From the “1997 Nobel Prizes in Science, The Mechanism of Life” by Staff Editor Copyright © 1998 by Scientific American, Inc All rights reserved Chapter 11 Cover—Image credited to Bernd Juergens From Shutterstock Chapter 12 Cover—Image credited to O2 creationz From Shutterstock Figure 12.8—Image credited to Michael Feldman, MD, PhD From Wikimedia Commons Copyright © 2005 Used under license: CC-BY-2.0 ... preventing formation of supercoils, as described in Chapter 6 of MCAT Biochemistry Review This step is important in allowing the transcriptional machinery access to the DNA and the particular gene of interest Transcription... codon on an mRNA molecule while in the ribosome There are 20 amino acids in eukaryotic proteins, each of which is represented by at least one codon To become part of a nascent polypeptide in the ribosome, amino acids are... Change in DNA Sequence Effect on Encoded Protein Silent (degenerate) Missense Nonsense 7 .2 Transcription LEARNING GOALS After Chapter 7 .2, you will be able to: Explain how each of the eukaryotic RNA polymerases (I, II, and III)