Lippincott's Illustrated Reviews Biochemistry Series Editor: Richard A.Harvey 5th edition Richard Harvey Denise Ferrier .Wolters Kluwer
Harvey Ferrier Lippincott’s Illustrated Reviews LWW.com 5th edition Lippincott’s Illustrated Reviews Richard Harvey Denise Ferrier Series Editor: Richard A. Harvey 5th edition Biochemistry—USMLE Review Figure 3.20 Molecular and cellular events leading to sickle cell crisis. Biochemistry 5th edition Richard A. Harvey Denise R. Ferrier Lippincott’s Illustrated Reviews Lippincott’s Illustrated Reviews: Biochemistry is the long-established, fi rst-and-best resource for the essentials of biochemistry. Students rely on this text to help them quickly review, assimilate, and integrate large amounts of critical and complex information. For more than two decades, faculty and students have praised LIR Biochemistry’s matchless illustrations that make concepts come to life. Get fully prepared for coursework and board exams with these hallmark features from Lippincott’s Illustrated Reviews: ✓ Outline format – perfect for both concise review and foundational learning. ✓ Annotated, full-color illustrations – visually explain complex biochemical processes. ✓ Chapter overviews and summaries – reinforce your study time! ✓ Clinical boxes – take students quickly from the classroom to the patient, associating key concepts with real-world scenarios. ✓ Cross-references within this book, and to other disciplines in the series. ✓ More than 100 review questions included in the book! ✓ Free With Purchase!!! A comprehensive online exam featuring an additional 450 practice questions, plus fully searchable online text! Additional FREE!! Online resources available on , where Teaching, Learning, and Technology “click.” Don’t miss these other titles in the Lippincott’s Illustrated Reviews series: LIR: Immunology • LIR: Microbiology LIR: Pharmacology • LIR: Cell and Molecular Biology Don’t miss these other titles in the Lippincott’s Illustrated Reviews series: LIR: Immunology • LIR: Microbiology LIR: Pharmacology • LIR: Cell and Molecular Biology Lippincott’s Illustrated Reviews—Seeing is Understanding
Contents UNIT I:Protein Structure and Function a Enzymes UNIT I:Intermediary Metabolism Chapter 6:Bioenergetics and Oxidative Phosphorylation 69 Chapter 7:Introduction to Carbohydrates 83 Chapter 8:Glycolysis 91 Chapter 9:Tricarboxylic Acid Cycle 109 Chapter 10:Gluconeogenesis 117 Chapter 11:Glycogen Metabolism 125 Chapter 12:Metabolism of Monosaccharides and Disaccharides 137 Chapter 13:Pentose Phosphate Pathway and NADPH 145 Chapter 14:Glycosaminoglycans,Proteoglycans,and Glycoproteins 157 UNIT II:Lipid Metabolism Chapter15:Metabolism of Dietary Lipids 173 Chapter 16:Fatty Acid and Triacylglycerol Metabolism 181 Chapter 17:Complex Lipid Metabolism 201 Chapter 18:Cholesterol and Steroid Metabolism 219 TTIW入Nitw n metabolism sal of Nitrogen 245 Chapter 20:Amino Acid De 261 Chapter 21:Co Chapter 22:Nucleotide Metabolism 291 UNIT V:Integration of Metabolism Chapter 23:Metabolic Effects of Insulin and Glucagon 307 Chapter 24:The Feed/Fast Cycle 321 Chapter 25:Diabetes Mellitus 337 Chapter 26:Obesity 349 Chapter 27:Nutrition 357 Chapter 28:Vitamins 373 Chapter 29 Structure,Replication and Repair 395 Chapter 30 Chapter 31 Protein Synth Chapter 32 Regulation of Gene Expression 449 Chapter 33:Biotechnology and Human Disease 465 Index 489
Contents UNIT I: Protein Structure and Function Chapter 1: Amino Acids 1 Chapter 2: Structure of Proteins 13 Chapter 3: Globular Proteins 25 Chapter 4: Fibrous Proteins 43 Chapter 5: Enzymes 53 UNIT II: Intermediary Metabolism Chapter 6: Bioenergetics and Oxidative Phosphorylation 69 Chapter 7: Introduction to Carbohydrates 83 Chapter 8: Glycolysis 91 Chapter 9: Tricarboxylic Acid Cycle 109 Chapter 10: Gluconeogenesis 117 Chapter 11: Glycogen Metabolism 125 Chapter 12: Metabolism of Monosaccharides and Disaccharides 137 Chapter 13: Pentose Phosphate Pathway and NADPH 145 Chapter 14: Glycosaminoglycans, Proteoglycans, and Glycoproteins 157 UNIT III: Lipid Metabolism Chapter 15: Metabolism of Dietary Lipids 173 Chapter 16: Fatty Acid and Triacylglycerol Metabolism 181 Chapter 17: Complex Lipid Metabolism 201 Chapter 18: Cholesterol and Steroid Metabolism 219 UNIT IV: Nitrogen Metabolism Chapter 19: Amino Acids: Disposal of Nitrogen 245 Chapter 20: Amino Acid Degradation and Synthesis 261 Chapter 21: Conversion of Amino Acids to Specialized Products 277 Chapter 22: Nucleotide Metabolism 291 UNIT V: Integration of Metabolism Chapter 23: Metabolic Effects of Insulin and Glucagon 307 Chapter 24: The Feed/Fast Cycle 321 Chapter 25: Diabetes Mellitus 337 Chapter 26: Obesity 349 Chapter 27: Nutrition 357 Chapter 28: Vitamins 373 UNIT VI: Storage and Expression of Genetic Information Chapter 29: DNA Structure, Replication and Repair 395 Chapter 30: RNA Structure, Synthesis and Processing 417 Chapter 31: Protein Synthesis 431 Chapter 32: Regulation of Gene Expression 449 Chapter 33: Biotechnology and Human Disease 465 Index 489 168397_P00i-viii.qxd7.0:00 Front Matter 10-11-05 2010.4.4 10:50 AM Page vii
UNIT I: Protein Structure and Function Amino Acids I.OVERVIEW Free amino acid Proteins are the most abundant and functionally diverse molecules in ly every Common to reulate metabolism in the body.whereas contractile proteins in muscle permit movement.In bone,the protein collagen forms a framework for of calcium phosphate cryst acting like the stee COOH hemoglobin and plasma albumin.shuttle to whereas immunoglobulins fight infectious bacteria and viruses.In short, R ature of b ing near how these simple building blocks are ioined to form proteins thaave chain o-Carbon is unique three-dimensional structures,making them capable of perform- h an ng specific b logic functions. acid mino groups. ine IL.STRUCTURE OF THE AMINO ACIDS Although more than 300 different amino acids have been described in NH-CH-CO-NH-CH-CO nature,only 20 are commonly found as constituents of mammalian pro iens.Note:Theeairth e only amino ac shat are coded for by DNA hich has a primary amino group,and a distinctive side chain("R-group)bonded e cha m(re.A At physo H the car boxyl rming th (NH.In proteins.aimost all of these carboxyl and amino groups are Figure 1.1 combined through peptide linkage and,in general,are not available for m exce ogen b e ne chains tha
Amino Acids 1 I. OVERVIEW Proteins are the most abundant and functionally diverse molecules in living systems. Virtually every life process depends on this class of molecules. For example, enzymes and polypeptide hormones direct and regulate metabolism in the body, whereas contractile proteins in muscle permit movement. In bone, the protein collagen forms a framework for the deposition of calcium phosphate crystals, acting like the steel cables in reinforced concrete. In the bloodstream, proteins, such as hemoglobin and plasma albumin, shuttle molecules essential to life, whereas immuno globulins fight infectious bacteria and viruses. In short, proteins display an incredible diversity of functions, yet all share the common structural feature of being linear polymers of amino acids. This chapter describes the properties of amino acids. Chapter 2 explores how these simple building blocks are joined to form proteins that have unique three-dimensional structures, making them capable of performing specific biologic functions. II. STRUCTURE OF THE AMINO ACIDS Although more than 300 different amino acids have been described in nature, only 20 are commonly found as constituents of mammalian proteins. [Note: These are the only amino acids that are coded for by DNA, the genetic material in the cell (see p. 395).] Each amino acid (except for proline, which has a secondary amino group) has a carboxyl group, a primary amino group, and a distinctive side chain (“R-group”) bonded to the α-carbon atom (Figure 1.1A). At physiologic pH (approximately pH 7.4), the carboxyl group is dissociated, forming the negatively charged carboxylate ion (–COO– ), and the amino group is protonated (–NH3 +). In proteins, almost all of these carboxyl and amino groups are combined through peptide linkage and, in general, are not available for chemical reaction except for hydrogen bond formation (Figure 1.1B). Thus, it is the nature of the side chains that ultimately dictates the role Figure 1.1 Structural features of amino acids (shown in their fully protonated form). C +H3N NH-CH-COCOOH C H +H3N COOH H Common to all α-amino acids of proteins Free amino acid Amino acids combined through peptide linkages R R NH-CH-CO R Amino group Carboxyl group Cα H Carboxyl group α Amino R group R Side chain is distinctive for each amino acid. α-Carbon is between the carboxyl and the amino groups. R R Side chains determine properties of proteins. A B 1 UNIT I: Protein Structure and Function 168397_P001-012.qxd7.0:02 Protein structure 5-20-04 2010.4.4 9:45 AM Page 1
2 1.Amino Acids an amino acid plays in a protein.It is,therefore,useful to classify the amino acids according to the properties of their side chains,that is, whe etner they are nonpol A.Amino acids with nonpolar side chains Each of these amino acids has a nonpolar side chain that does not gain or lose protons or participate in hydrogen or ionic bonds (Figure 1.2).The side chains of these amino acids can be thought of NONPOLAR SIDE CHAINS 00H-pK,=23 COOH COOH 'HgN-C -H "HgN- -H 'HgN-C-H CH pk=9.6 HaC CHa Glycine Alanine Valine COOH COOH COOH H N-C-H 'HgN C-H +HaN-C-H CH> H-C-CHg CH HaC CHa Leucine COOH COOH -HgN- C-H CH2 Tryptophan Methionine Proline Figure 1.2 ciab for the x-amino onated groups onpo
an amino acid plays in a protein. It is, therefore, useful to classify the amino acids according to the properties of their side chains, that is, whether they are nonpolar (have an even distribution of electrons) or polar (have an uneven distribution of electrons, such as acids and bases; Figures 1.2 and 1.3). A. Amino acids with nonpolar side chains Each of these amino acids has a nonpolar side chain that does not gain or lose protons or participate in hydrogen or ionic bonds (Figure 1.2). The side chains of these amino acids can be thought of as “oily” or lipid-like, a property that promotes hydro phobicinter - actions (see Figure 2.10, p. 19). 1. Location of nonpolar amino acids in proteins: In proteins found in aqueous solutions––a polar environment––the side chains of the nonpolar amino acids tend to cluster together in the interior of the protein (Figure 1.4). This phenomenon, known as the hydrophobic C +H3N COOH H H pK2 = 9.6 pK1 = 2.3 Glycine C +H3N COOH H CH3 Alanine Valine C +H3N COOH H CH2 Methionine CH2 C +H3N COOH H CH2 Phenylalanine C +H3N COOH H CH2 Tryptophan C CH N H S CH3 COOH H Proline C CH2 +H2N CH2 H2C NONPOLAR SIDE CHAINS Figure 1.2 Classification of the 20 amino acids commonly found in proteins, according to the charge and polarity of their side chains at acidic pH is shown here and continues in Figure 1.3. Each amino acid is shown in its fully protonated form, with dissociable hydrogen ions represented in red print. The pK values for the α-carboxyl and α-amino groups of the nonpolar amino acids are similar to those shown for glycine. (Continued in Figure 1.3.) C +H3N COOH H CH H3C CH3 C +H3N COOH H CH2 Leucine CH H3C CH3 C +H3N COOH H CH3 H CH C 3 CH2 Isoleucine 2 1. Amino Acids 168397_P001-012.qxd7.0:02 Protein structure 5-20-04 2010.4.4 9:45 AM Page 2
Il.Structure of the Amino Acids UNCHARGED POLAR SIDE CHAINS C00HK1=22 COOH COOH 'HgN-C-H 'HgN-C-H pK2=9. H-C-OH H-C-OH 0HpK=10.1 Serine Threonine Tyrosine COOH COOH 'HgN-C-H 'HgN-C-H Co0H·pK,=17 % CHa pk=08 SH--pK2=8.3 Asparagine Glutamine Cysteine ACIDIC SIDE CHAINS pK,=21 COOH pK=98 pK3=9.7--HgN-C CH, CH, pK2=39 pk2=4.3 Aspartic acid BASIC SIDE CHAINS pK=22 pK=92 pK2=92 COOH pK29.0 COOH 'HjN-C -H 'HgN-C-H CH2 CH2 CH2 K2=6.0 -pK3=10.5 pK3=125 Histidine Lysine Arginine Figure 1.3 Stiosa8atsea8de8月rsn0eroHadyetnsacordng1ohechargeandpoaiy
C +H3N COOH H CH2 O OH CH2 C ACIDIC SIDE CHAINS pK1 = 2.1 pK2 = 4.3 C pK3 = 9.7 +H3N COOH CH2 Aspartic acid O OH C pK2 = 3.9 pK3 = 9.8 C +H3N CH2 CH2 BASIC SIDE CHAINS C +H3N CH2 pK3 = 9.2 CH NH C H +HN C pK2 = 6.0 CH2 CH2 NH3 + pK3 = 10.5 C +H3N CH2 CH2 CH2 N pK3 = 12.5 H C NH2 NH2 + C +H3N H CH2 O NH2 C +H3N CH2 Asparagine Glutamine O NH2 CH2 C UNCHARGED POLAR SIDE CHAINS C +H3N COOH H CH2 Cysteine SH pK3 = 10.8 pK2 = 8.3 pK1 = 1.7 C +H3N COOH H Serine C H H OH C +H3N Threonine C CH3 H OH C +H3N COOH H CH2 Tyrosine OH pK2 = 9.1 pK3 = 10.1 pK1 = 2.2 C CH2 C ACIDIC SIDE CHAINS H O C pK2 = 3.9 C +H3N COOH H CH2 CH2 BASIC SIDE CHAINS pK1 = 2.2 C +H3N COOH H CH2 Histidine pK3 = 9.2 CH NH C H +HN C pK1 = 1.8 pK2 = 6.0 CH2 CH2 NH3 + pK3 = 10.5 Lysine pK2 = 9.0 C +H3N COOH H CH2 CH2 CH2 N pK3 = 12.5 Arginine H C NH2 NH2 + C +H3N COOH C +H3N COOH H CH2 O NH2 CH2 C UNCHARGED POLAR SIDE CHAINS CH2 C C OH C +H3N COOH H C CH3 H OH +H3N Tyrosine pK3 = 10.1 C Figure 1.3 Classification of the 20 amino acids commonly found in proteins, according to the charge and polarity of their side chains at acidic pH (continued from Figure 1.2). pK2 = 9.2 II. Structure of the Amino Acids 3 168397_P001-012.qxd7.0:02 Protein structure 5-20-04 2010.4.4 9:45 AM Page 3