Đang tải... (xem toàn văn)
(BQ) Part 1 book Netter’s essential biochemistry hass contents: Human karyotype and the structure of DNA, basic genetics for biochemistry, cell cycle and cancer, enzymes and consequences of enzyme deficiencies, biological membranes,... and other contents.
Place Peel Off Sticker Here NETTER: It’s How You Know Anatomy Netter Collection of Medical Illustrations, 2nd Edition Entire Collection Now Available! The Netter Collection of Medical Illustrations, Dr Frank H Netter’s decades of work devoted to depicting each of the major body systems, has been updated and brought into modern context The second edition of the legendary “green books” offers Netter’s timeless work, now arranged and enhanced by modern text and radiologic imaging Contributions by eld-leading doctors and teachers from world-renowned medical institutions are supplemented with new illustrations created by master artist-physician Carlos Machado and other top medical illustrators working in the Netter tradition Netter’s Correlative Imaging Series The Netter’s Correlative Imaging series pairs classic Netter and Netter-style illustrations with imaging studies and succinct descriptions to provide you with a richer understanding of human anatomy These comprehensive, normal anatomy atlases cover all major sections of the body, featuring illustrated plates side-by-side with the most common imaging modalities for each region Shop online at elsevierhealth.com Explore more essential resources in the NETTER BASIC SCIENCE COLLECTION! Netter’s Essential Histology With Student Consult Access By William K Ovalle, PhD, and Patrick C Nahirney, PhD Bring histologic concepts to life through beautiful Netter illustrations! Netter’s Atlas of Neuroscience With Student Consult Access By David L Felten, MD, PhD, M Kerry O’Banion, MD, PhD, and Mary Summo Maida, PhD Master the neuroscience fundamentals needed for the classroom and beyond Netter’s Essential Physiology With Student Consult Access By Susan E Mulroney, PhD, and Adam K Myers, PhD Enhance your understanding of physiology the Netter way! Netter’s Atlas of Human Embryology With Student Consult Access By Larry R Cochard, PhD A rich pictorial review of normal and abnormal human prenatal development Netter’s Introduction to Imaging With Student Consult Access By Larry R Cochard, PhD, et al Finally an accessible introduction to diagnostic imaging! Netter’s Illustrated Human Pathology With Student Consult Access By L Maximilian Buja, MD, and Gerhard R F Krueger, PhD Gain critical insight into the structure-function relationships and the pathological basis of human disease! Netter’s Illustrated Pharmacology With Student Consult Access By Robert B Raffa, PhD, Scott M Rawls, PhD, and Elena Portyansky Beyzarov, PharmD Take a distinct visual approach to understanding both the basic science and clinical applications of pharmacology Shop online at elsevierhealth.com NETTER’S ESSENTIAL BIO CHEMISTRY PETER RONNER, PhD Pro essor o Biochemistry and Molecular Biology Pro essor o Pharmaceutical Sciences Department o Biochemistry and Molecular Biology T omas Jef erson University Philadelphia, Pennsylvania Illustrations by Frank H Netter, MD Contributing Illustrators Carlos A.G Machado, MD James A Perkins, MS, MFA Kip Carter, MS, CMI if any Davanzo, MA, CMI 1600 John F Kennedy Blvd Ste 1800 Philadelphia, PA 19103-2899 NE ER’S ESSEN IAL BIOCHEMIS RY Copyright © 2018 by Elsevier, Inc All rights reserved ISBN: 978-1-929007-63-9 No part o this publication may be reproduced or transmitted in any orm or by any means, electronic or mechanical, including photocopying, recording, or any in ormation storage and retrieval system, without permission in writing rom the publisher Details on how to seek permission, urther in ormation about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be ound at our website: www.elsevier.com/permissions T is book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Permission or Netter Art gures may be sought directly rom Elsevier’s Health Science Licensing Department in Philadelphia, PA: phone 800-523-1649, ext 3276, or 215-239-3276; or email H.licensing@elsevier.com Notices Knowledge and best practice in this eld are constantly changing As new research and experience broaden our understanding, changes in research methods, pro essional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any in ormation, methods, compounds, or experiments described herein In using such in ormation or methods they should be mind ul o their own sa ety and the sa ety o others, including parties or whom they have a pro essional responsibility With respect to any drug or pharmaceutical products identi ed, readers are advised to check the most current in ormation provided (i) on procedures eatured or (ii) by the manu acturer o each product to be administered, to veri y the recommended dose or ormula, the method and duration o administration, and contraindications It is the responsibility o practitioners, relying on their own experience and knowledge o their patients, to make diagnoses, to determine dosages and the best treatment or each individual patient, and to take all appropriate sa ety precautions o the ullest extent o the law, neither the Publisher nor the authors, contributors, or editors, assume any liability or any injury and/or damage to persons or property as a matter o products liability, negligence or otherwise, or rom any use or operation o any methods, products, instructions, or ideas contained in the material herein Library o Congress Cataloging-in-Publication Data Names: Ronner, Peter, 1951- author | Netter, Frank H (Frank Henry), 1906-1991, illustrator | Machado, Carlos A G., illustrator | Craig, John A., illustrator | Perkins, James A., illustrator itle: Netter’s biochemistry / Peter Ronner ; illustrations by Frank H Netter ; contributing illustrators, Carlos A.G Machado, John A Craig, James A Perkins Other titles: Biochemistry Description: Philadelphia, PA : Elsevier, [2018] | Includes bibliographical re erences and index Identi ers: LCCN 2016024484 | ISBN 9781929007639 (pbk : alk paper) Subjects: | MESH: Biochemical Phenomena | Biochemistry Classi cation: LCC QP514.2 | NLM QU 34 | DDC 572–dc23 LC record available at https://lccn.loc.gov/2016024484 Executive Content Strategist: Elyse O’Grady Content Development Specialist: Stacy Eastman Publishing Services Manager: Patricia annian Senior Project Manager: Carrie Stetz Design Direction: Julia Dummitt Printed in China Last digit is the print number: o Wanda and Lukas Abo ut the Autho r Peter Ronner, PhD, is Pro essor o Biochemistry and Molecular Biology at the Sidney Kimmel College o Medicine at T omas Jef erson University in Philadelphia He holds a secondary appointment as Pro essor o Pharmaceutical Sciences in the College o Pharmacy at T omas Jef erson University Dr Ronner received his PhD in Biochemistry rom the Swiss Federal Institute o echnology (E H) in Zurich His ormer laboratory research involved studies o pancreatic hormone secretion Dr Ronner has taught medical students or nearly 30 years and pharmacy students or almost 10 years He is also a past chair o the Association o Biochemistry Course Directors (now Association o Biochemistry Educators) At Jef erson, he has received numerous awards or his teaching, including a Lindback Award and a portrait painting vi Pentos e Phos phate Pathway, Oxidative Stres s , and Glucos e 6-Phos phate Dehydrogenas e De ciency ree iron, this minimizes the production o •OH •OH cannot be ef ectively removed by an enzyme because it reacts be ore it could dif use to an enzyme •OH and the lipid radicals it gives rise to are removed to some degree by glutathione, which is ubiquitous Glutathione also removes lipid radicals (2 GSH + •lipid → GSSG + lipid) Fig 21.7 shows how the at-soluble vitamin E, ascorbate, glutathione, and NADPH work together in a chain to react with various lipid radicals Degradation o cyclized lipid peroxyl radicals yields malondialdehyde, which in turn crosslinks proteins and/or lipids (see Fig 21.6) In clinical research, the concentration o circulating malondialdehyde is sometimes used as a measure o oxidative damage T e terms antioxidant and ree radical scavengers are used synonymously or compounds that react with oxidants by donating at least one H with its one electron Antioxidants are requently divided into at-soluble and water-soluble compounds T e major at-soluble antioxidants in the human body are: ■ ■ ■ ■ ■ Vitamin E Carotenes, including vitamin A, β-carotene (in carrots, pumpkins), and lycopene (in tomatoes) Coenzyme QH2 (ubiquinol) is ound in all membranes, reacts with ROS, and thereby protects unsaturated atty acids in membranes Ubiquinol is also part o the electron transport chain (see Chapter 23) in the inner mitochondrial membrane Dihydrolipoic acid is active both in the cytosol and in membranes Lipoic acid (see Fig 22.5) is sometimes used in the treatment o pain ul diabetic neuropathy Cells reduce exogenous lipoic acid to the antioxidant dihydrolipoic acid T e R(+) enantiomer o lipoic acid also serves as a reversibly reduced prosthetic group o pyruvate dehydrogenase, α -ketoglutarate dehydrogenase, and branchedchain ketoacid dehydrogenase Bilirubin is a degradation product o heme that circulates in blood as part o its transport rom the spleen to the liver (see Chapter 14) T e major water-soluble antioxidants include: ■ ■ ■ Ascorbate Glutathione Uric acid, which pre erentially reacts with peroxynitrite, the product o a reaction between superoxide anion and nitric oxide Finally, the body’s de ense against oxidative damage also includes the repair o damage to DNA and proteins DNA base excision repair repairs 8-oxo-guanine in DNA (see Section in Chapter 2), which is the predominant DNA base damage in icted by ROS ( rom •OH, reacting with guanine) T e concentration o 8-oxo-guanine can be used as a measure o a cell’s stress Damage to proteins rom ROS and hypochlorous acid af ects mostly cysteine and methionine residues; this can lead to the ormation o cysteine disul des and methionine 229 sul oxide, or example T ioredoxin- or glutaredoxindependent enzymes reduce disul de bonds (–S–S–) Methionine sul oxide reductase reduces methionine sul oxide Other types o damage o en remain unrepaired and are dealt with by the ongoing degradation o proteins and concurrent synthesis o new proteins GLUCOSE 6-PHOSPHATE DEHYDROGENASE DEFICIENCY A def ciency o G6PD is a common X-linked disorder that is prevalent in populations originating rom certain regions where malaria has been, or still is, endemic It is marked by an increased incidence o neonatal jaundice and then, throughout li e, by susceptibility to hemolysis a er oxidative stress De ciency o G6PD (see Section 1) is very common in populations originating rom parts o the world where malaria has been or still is endemic (i.e., equatorial A rica, Middle East, Mediterranean, and Southeast Asia; see Fig 17.1) T e reason or this nding is that G6PD-de cient persons are less likely to have severe malaria About 5% to 25% o people rom the above populations have one o the variant alleles with low G6PD activity T e gene is located on the X chromosome; males are more requently symptomatic than emales Low G6PD activity limits production o NADPH and maintenance o GSH (glutathione), thereby impairing the de ense against oxidative stress (see Section 2) A total lack o the enzyme is lethal When G6PD-de cient erythrocytes experience excessive oxidative damage due to impaired de ense against ROS, they hemolyze in the bloodstream (intravascular hemolysis) and give rise to hematuria In unaf ected persons, only a small number o red blood cells normally lyse in the bloodstream, and most erythrocytes are instead cleared by the spleen and liver (see Chapter 14) In G6PD-de cient persons, the hemolysis is more extensive than normal and can lead to anemia and jaundice Some patients with severe disease require a trans usion o resh red blood cells O en, Heinz bodies (aggregates o damaged globin) accumulate inside red blood cells o G6PD-de cient individuals who experience increased oxidative stress Heinz bodies are detected by microscopic observation o a stained blood smear T e hemolysis resolves once the oxidizing substance that triggered the attack is removed About 140 mutations in the G6PD gene are known, which explains in part the variation in patient response to oxidative stress A variant called G6PD A– is common in people whose origin is in A rica T e variant entails two point mutations that lead to the amino acid substitutions Val68Met and Asn126Asp G6PD Mediterranean is common in people rom the Mediterranean, the Middle East, and India; it entails a point mutation that leads to a Ser188Phe substitution T e large majority o G6PD variants af ects the stability o the G6PD protein T ese variants have minimal ef ect on cells that continuously synthesize new G6PD However, the instability o G6PD 230 Pentos e Phos phate Pathway, Oxidative Stres s , and Glucos e 6-Phos phate Dehydrogenas e De ciency G6P D a ctivity in 1502 males 400 400 n a t e 300 n e o 250 r o f 200 m b e 150 u 100 N e t a n o e n f o r e b m u s 350 s 350 N G6P D a ctivity in 1298 fe ma les 300 250 200 150 100 50 50 0 30 G6PD e nzyme ac tivity units /g Hb Hemizygous deficient 30 G6PD e nzyme ac tivity units /g Hb Homozygous de ficie nt Hemizygous normal Homozygous norma l Hete rozygous for deficie ncy Fig 21.8 G6PD ac tivity in male and fe male ne wbo rns G6PD activity was meas ured in newborns of Sephardic J ewis h ethnicity, a group in which G6PD de ciency is common Blue and red arrows indicate approximate ranges (Modi ed from Algur N, Avraham I, Hammerman C, Kaplan M Quantitative neonatal glucos e-6-phos phate dehydrogenas e s creening: dis tribution, reference values , and clas s i cation by phenotype J Pediatr 2012;161:197-200.) af ects red blood cells, which cannot synthesize new G6PD molecules (mature erythrocytes not have DNA, RNA, or ribosomes) Severe G6PD de ciency can also impair the unction o peripheral nerves, perhaps due to loss o G6PD activity during transport in axons Since emales show patchy, random X-inactivation, heterozygous emales show a broad range o approximately intermediate G6PD activity that eludes easy classi cation (Fig 21.8) G6PD-de cient newborns are at increased risk or neonatal jaundice (see Chapter 14) and its complications Severe hyperbilirubinemia leads to brain damage Many cases o severe neonatal hyperbilirubinemia are due to a G6PD de ciency Hence, all newborns who are at risk o G6PD de ciency due to parental carrier status or ethnic background should have their bilirubin levels monitored closely Erythrocytes o G6PD-de cient individuals may hemolyze during an in ection, such as during pneumonia, hepatitis B, or symptomatic in ection with cytomegalovirus (a herpes virus) A er ingestion o ava beans (also called broad beans), erythrocytes o G6PD-de cient persons may hemolyze Fava beans ( rom the plant Vicia aba) contain vicine, which is an oxidizing agent Hemolysis precipitated by ava beans has been known since antiquity and has been re erred to as avism Oxidative drugs that predictably cause hemolysis in patients with at least mild G6PD de ciency are primaquine and dapsone (used as antimalarials), methylene blue (used to treat methemoglobinemia), phenazopyridine (used as an analgesic and antipyretic), and the H 2O2-producing uricases, such as rasburicase and pegloticase (used mostly in the treatment o tumor lysis syndrome and in gout that cannot be treated with other drugs) Severe hemolysis can lead to acute Table 21.1 WHO Clas s i c atio n o f G6PD De c ie nc y G6PD Ac tivity, % o f No rmal Clas s He mo lys is I Chronic