Textbook of Biochemistry with Clinical Correlations 7e (www.medsmart.ir)

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Textbook of

BIOCHEMISTRY

With Clinical Correlations

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Textbook of

BIOCHEMISTRY

With Clinical Correlations EDITED BY

Thomas M. Devlin Professor Emeritus Department ofBiochemistry and Molecular Biology College ofMedicine Drexel Universiry

John Wiley & Sons, Inc.

IMAGE ON FRONT COVER Model of a p artial telomerase elongation complex. The enzyme relomerase is a ribonudeoprorein reverse cranscriprase

responsible for maintaining the length and integriry of the ends of linear chromosomes, rermed relomeres, present in eu­ karyotes. The figure depicrs the partial scrucrure of the relomerase elongation complex ar the end of a chromosome (blue spheres). The catalytic subunit of telomerase (red rods) uses an integral RNA template (green spheres) co add multiple identical repeats of deoxyribonudeotides co the 3' end of the DNA scrand of the chromosome. Telomerase and relomere dysfunction are considered co concribure co replicative senescence and programmed cell aging. Activation of telomerase is associated with the uncontrollable prolifecarion of cells found in about 85 percent of human cancers. A discussion of celomerase is presented in chapter 4. Gillis, A, J., Schuller, A. P., Skordalakes, E. Scructure of the Tribolium castaneum celomerase caralyric subunit TERT. Nature 455:633, 2008. Figure generously supplied by Dr. Emmanuel Skordalakes, The Wiscar Institute, Philadelphia, PA 19104, USA PUBLISHER ASSOCIATE PUBLISHER ACQUISITIONS EDITOR EDITORIAL ASSISTANT SENIOR PRODUCTION AND MANUFACTURING MANAGER SENIOR PRODUCTION EDITOR MARKETING MANAGER SENIOR DESIGNER INTERIOR DESIGNER COVER DESIGNER SENIOR ILLUSTRATION EDITOR EXECUTIVE MEDIA EDITOR MEDIA EDITOR

KAYE PACE PETRA RECTER JOAN KALKUT YELENA ZOLOTOREVSKAYA MICHELINE FREDERICK KERRY WEINSTEIN KRISTINE RUFF KEVIN MURPHY LAURA IERARDI M77 DESIGN SANDRA RIGBY TOM KULESA MARC WEZDECKI

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Textbook of biochemisrry : with clinical correlations / edired by Thomas M. Devlin. - 7th ed. p.;cm.

Includes bibliographical references and index. ISBN 978-0-470-28173-4 (cloth) BRV ISBN 978-0-470-60152-5 1. Biochemistry. 2. Clinical biochemistry. I. Devlin, Thomas M. II. Title: Biochemistry. [DNLM: I. Biochemical Phenomena. QU 4 T355 2010) QP514.2.T4 2010 612'.015-dc22 Printed in rhe United Scares of America 10 9 8 7 6 5 4 3 2 1

2009046304

• TO MY FAMILY Steve, Bonnie, Mark, Cathy, Kate, Matt, Ryan, and Laura who have been constant sources of pride and love and

• TO MARJORIE who has been with me through seven editions for her enduring encouragement, support, and love

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Proteins I: Composition and Structure Richard M. Schultz Professor, Stritch School ofMedicine, Loyola University ofChicago

3.1 • FUNCTIONAL ROLES OF PROTEINS IN HUMANS 76

3.2 • AMINO ACID COMPOSITION OF PROTEINS 76

3.3 • CHARGE AND CHEMICAL PROPERTIES OF AMINO ACIDS AND PROTEINS 82 3.4 • PRIMARY STRUCTURE OF PROTEINS 90

3. 7 • FOLDING OF PROTEINS FROM RANDOMIZED TO UNIQUE STRUCTURES: PROTEIN STABILITY 112

3.8 • DYNAMIC ASPECTS OF PROTEIN STRUCTURE 120

3.9 • CHARACTERIZATION,

PURIFICATION, AND DETERMINATION OF PROTEIN STRUCTURE AND ORGANIZATION 121

3.5 • HIGHER LEVELS OF PROTEIN ORGANIZATION 92

3.6 • NONGWBULAR STRUCTURED

CLINICAL CORRELATIONS 3.1 Plasma Prote ins in Diagnosis

of Disease 87 3.2 Differences in Insulins Used in Treatment of Diabetes Mellitus 92 3.3 Hyperlipoproteinemias 109 3.4 Hypolipoproteinemias 110 3.5 Glycosylated Hemoglobin, HbA 1c 113 3.6 Prion Diseases and Proteins as Infectious Agents: Human Transmissible Spongiform Encephalopathies (TSEs) 114 3.7 Use of Amino Acid Analysis in Diagnosis of Disease 127

PROTEINS 103

Key Concepts • Two types of amino acids compose polypeptides: common and derived amino acids. Common amino acids have a central carbon atom to which is attached an amino group, a carboxylic acid group, a hydrogen atom, and a side­ chain group. • Amino acids in polypeptide chains are joined by a peptide bond that connects the a-carboxylic acid group of one amino acid with the a-amino group of a second amino acid. • Amino acids and proteins have acid-base and related charge properties that determine their biological activity and are used for characterization and purification. • A protein is defined by its secondary, tertiary, and quaternary structure. a-Helical and /3-structures are common stable second ary structures found in folded proteins. • Globular proteins domains are formed from structural motifs and characteristic folds.

• Proteins in cells are present in complexes that are organized in nerworks and participate in interactomes. • Some proteins are intrinsically unstructured, which is required for their biological functions. • Nonglobular proteins include fibrous proteins such as collagen with characteristic repeating amino acid sequence and unusual helix and rod-shaped geometry. • A protein folds to its conformation of lowest Gibbs free energy, within kinetic constraints, under the control of noncovalent forces. • Folded protein structures are dynamic with atoms fluctuating and rotating around an average position. • Proteins are purified and characterized by techniques that utilize charge and molecular weight. Protein structure is characterized by spectral, optical, and X-ray diffraction techniques. • Proteomic techniques determine the expression of thousands of proteins within a cell or tissue in a single assay.

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