Essentials of Medical Biochemistry - N. V. Bhagavan, Chung Eun Ha

Essentials of Medical Biochemistry (eBook)

With Clinical Cases

N. V. Bhagavan, Chung Eun Ha (Autoren)

eBook Download: PDF | EPUB

2011 | 1. Auflage
600 Seiten
Elsevier Science (Verlag)
978-0-08-091688-0 (ISBN)

Expert biochemist R.V. Bhagavan's new work condenses his successful Medical Biochemistry texts along with numerous case studies, to act as an extensive review and reference guide for both students and experts alike. The research-driven content includes four-color illustrations throughout to develop an understanding of the events and processes that are occurring at both the molecular and macrolecular levels of physiologic regulation, clinical effects, and interactions. Using thorough introductions, end of chapter reviews, fact-filled tables, and related multiple-choice questions, Bhagavan provides the reader with the most condensed yet detailed biochemistry overview available. More than a quick survey, this comprehensive text includes USMLE sample exams from Bhagavan himself, a previous coauthor.

* Clinical focus emphasizing relevant physiologic and pathophysiologic biochemical concepts
* Interactive multiple-choice questions to prep for USMLE exams
* Clinical case studies for understanding basic science, diagnosis, and treatment of human diseases
* Instructional overview figures, flowcharts, and tables to enhance understanding

Expert biochemist N.V. Bhagavan's new work condenses his successful Medical Biochemistry texts along with numerous case studies, to act as an extensive review and reference guide for both students and experts alike. The research-driven content includes four-color illustrations throughout to develop an understanding of the events and processes that are occurring at both the molecular and macrolecular levels of physiologic regulation, clinical effects, and interactions. Using thorough introductions, end of chapter reviews, fact-filled tables, and related multiple-choice questions, Bhagavan provides the reader with the most condensed yet detailed biochemistry overview available. More than a quick survey, this comprehensive text includes USMLE sample exams from Bhagavan himself, a previous coauthor. Clinical focus emphasizing relevant physiologic and pathophysiologic biochemical concepts Interactive multiple-choice questions to prep for USMLE exams Clinical case studies for understanding basic science, diagnosis, and treatment of human diseases Instructional overview figures, flowcharts, and tables to enhance understanding

Front Cover 1
Essentials of Medical Biochemistry With Clinical Cases 4
Copyright Page 5
Contents 6
Preface 16
Acknowledgments 18
Chapter 1. Cells: Structure and Functions 20
Cells: Structures and Functions 20
Chapter 2. Water, Acids, Bases, and Buffers 28
Properties of Water 28
Buffers 31
H[sup(+)] Concentration and pH 36
Chapter 3. Amino Acids 38
L-& #945
Classification 39
Electrolyte and Acid–Base Properties 44
Chapter 4. Three-Dimensional Structure of Proteins 48
Covalent and Non-covalent Interactions 49
Primary Structure 50
Secondary Structure 50
Tertiary Structure 52
Quaternary Structure 53
Denaturation 53
Protein Folding and Associated Diseases 53
Chapter 5. Energetics of Biological Systems 58
Thermodynamics 59
Chemical Kinetics 63
Chapter 6. Enzymes and Enzyme Regulation 66
Nomenclature 66
Catalysis 67
Active Site and Enzyme–Substrate Complex 67
Michaelis–Menten Model for Enzyme-Catalyzed Reactions 68
Inhibition 70
Irreversible Inhibition 73
Chapter 7. Clinical Enzymology and Biomarkers of Tissue Injury 78
Diagnosis and Prognosis of Disease 78
Serum Markers in the Diagnosis of Tissue Damage 81
Enzymes as Analytical Reagents 83
Enzymes as Therapeutic Agents 83
Chapter 8. Simple Carbohydrates 84
Classification 85
Chapter 9. Heteropolysaccharides I: Glycoconjugates, Glycoproteins, and Glycolipids 94
Glycoproteins 94
Cell Membrane Constituents 97
Cell-Surface Glycoproteins 100
Serum Glycoproteins 101
Molecular Mimicry of Oligosaccharides and Host Susceptibility 102
Chapter 10. Connective Tissue: Fibrous and Non-Fibrous Proteins and Proteoglycans 104
Protein Fibers 105
Chapter 11. Gastrointestinal Digestion and Absorption 116
Anatomy and Physiology of the Gastrointestinal Tract 117
Gastrointestinal (GI) Hormones 121
Digestion and Absorption of Major Food Substances 122
Absorption of Water and Electrolytes 130
Thermic Effect of Food 132
Chapter 12. Carbohydrate Metabolism I: Glycolysis and the Tricarboxylic Acid Cycle 134
Glycolysis 134
Pyruvate Metabolism 144
Tricarboxylic Acid (TCA) Cycle 147
Chapter 13. Electron Transport Chain, Oxidative Phosphorylation, and Other Oxygen-Consuming Systems 154
Mitochondrial Structure and Properties 156
Oxidative Phosphorylation 161
The Mitochondrial Genome (see website) 165
Nuclear Control of Respiratory Chain Expression 166
Mitochondrial Diseases 166
Other Reducing-Equivalent Transport and Oxygen-Consuming Systems 166
Chapter 14. Carbohydrate Metabolism II: Gluconeogenesis, Glycogen Synthesis and Breakdown, and Alternative Pathways 170
Gluconeogenesis 171
Glycogen Metabolism 176
Alternative Pathways of Glucose Metabolism and Hexose Interconversions 181
Chapter 15. Protein and Amino Acid Metabolism 188
Essential and Nonessential Amino Acids 190
Metabolism of Ammonia 194
Metabolism of Some Individual Amino Acids 197
Chapter 16. Lipids I: Fatty Acids and Eicosanoids 210
Oxidation of Fatty Acids 211
Other Pathways of Fatty Acid Oxidation 217
Metabolism of Ketone Bodies 218
Synthesis of Long-Chain Saturated Fatty Acids 221
Metabolism of Unsaturated Fatty Acids 224
Trans-Fatty Acids 225
Essential Fatty Acids 225
Metabolism of Eicosanoids 225
Chapter 17. Lipids II: Phospholipids, Glycosphingolipids, and Cholesterol 228
Phospholipids 228
Phosphatidylcholines 229
Phosphosphingolipids 231
Phospholipids and Glycosphingolipids in Clinical Medicine 231
Cholesterol 233
Chapter 18. Lipids III: Plasma Lipoproteins 244
Structure and Composition 245
Metabolism 248
Chapter 19. Contractile Systems 260
Introduction 261
Muscle Systems 261
Non-Muscle Systems 273
Chapter 20. Perturbations of Energy Metabolism: Obesity and Diabetes Mellitus 280
Energy Metabolism 280
Chapter 21. Structure and Properties of DNA 294
Introduction 294
Chromosomes and Chromatin 300
Recombinant DNA Technology 301
Chapter 22. DNA Replication, Repair, and Mutagenesis 306
General Features of DNA Replication 306
The Enzymology of DNA Replication 308
DNA Mutations and DNA Repair 313
Chapter 23. RNA and Protein Synthesis 320
Structure of RNA 321
Messenger RNA 322
Enzymatic Synthesis of RNA 323
Prokaryotic Transcription 324
Transcription in Eukaryotes 325
Genetic Code 328
Attachment of Amino Acid to tRNA Molecule 329
Initiator tRNA Molecules and Selection of Initiation Codon 330
Ribosomes 330
Protein Synthesis 332
Chapter 24. Regulation of Gene Expression 340
Introduction 340
Regulation of mRNA Synthesis 340
Gene Regulation in Prokaryotes 341
Gene Regulation in Eukaryotes 345
Mechanisms of Gene Regulation in Eukaryotes 345
Chapter 25. Nucleotide Metabolism 352
One-Carbon Metabolism 352
Formation of 5-Phosphoribosyl-1-Pyrophosphate 355
Biosynthesis of Purine Nucleotides 356
Conversion of Nucleoside Monophosphates to Diphosphates and Triphosphates 358
Formation of Purine Deoxyribonucleotides 358
Regulation of Purine Biosynthesis 360
Inhibitors of Purine Biosynthesis 361
Catabolism of Purine Nucleotides 362
Disorders of Purine Nucleotide Metabolism 364
Biosynthesis of Pyrimidine Nucleotides 367
Coordination of Purine and Pyrimidine Nucleotide Biosynthesis 372
Catabolism of Pyrimidine Nucleotides 373
Abnormalities of Pyrimidine Metabolism 373
Chapter 26. Hemoglobin 374
Structure of Hemoglobins 375
Functional Aspects of Hemoglobin 376
Inherited Disorders of Hemoglobin Structure and Synthesis 381
Derivatives of Hemoglobin 385
Chapter 27. Metabolism of Iron and Heme 388
Iron Metabolism 388
Heme Biosynthesis 392
Disorders of Heme Biosynthesis 394
Heme Catabolism 395
Chapter 28. Endocrine Metabolism I: Introduction and Signal Transduction 402
Hormonal Amines 403
Peptide, Protein, and Glycoprotein Hormones 403
Steroid Hormones 404
Types of Hormone Receptors 406
Cell Surface Receptors 408
Chapter 29. Endocrine Metabolism II: Hypothalamus and Pituitary 416
Hypothalamus 416
Pituitary Gland (Hypophysis) 419
Chapter 30. Endocrine Metabolism III: Adrenal Glands 428
Synthesis of Corticosteroids 430
Adrenal Medulla 437
Chapter 31. Endocrine Metabolism IV: Thyroid Gland 444
Introduction 445
Thyroid Hormone Synthesis 445
Transport and Metabolism of Thyroid Hormones 449
Biological Actions of Thyroid Hormones 450
Chapter 32. Endocrine Metabolism V: Reproductive System 454
Sex Determination 455
Testes 456
Female Reproductive System 460
Chapter 33. Immunology 468
Introduction 468
Chapter 34. Biochemistry of Hemostasis 492
Hemostasis is a Two-Phase Process 492
Clotting Factors and the Coagulation Cascade 493
Clot Dissolution: Fibrinolysis 494
Protease Precursors 494
Cofactor Proteins 495
Protease Inhibitors 496
Other Proteins of the Hemostatic System 496
The Clotting Process and the Formation of Fibrin 497
Reactions of the Coagulation Cascade: The Procoagulant Subsystem 497
Activation of Prothrombin 498
The Extrinsic Pathway: Injury and Tissue Factor Exposure 498
The Anticoagulant Subsystem 499
Anticoagulant Subsystem: Protease Inhibitors 500
Fibrinolytic Subsystem 501
Vitamin K, Oral Anticoagulants, and Their Mechanisms of Action 502
Thrombosis: Hemostatic System Dysfunction 503
Chapter 35. Mineral Metabolism 506
Calcium and Phosphorus 506
Magnesium 518
Essential Trace Elements 518
Chapter 36. Vitamin Metabolism 522
Fat Soluble Vitamins 523
Water Soluble Vitamins 528
Chapter 37. Water, Electrolytes, and Acid-Base Balance 536
Water Metabolism 536
Homeostatic Controls 538
Water and Osmolality Controls 538
Electrolyte Balance 540
Acid–Base Balance 541
Chapter 38. Case Studies 546
Clinical Case Study 1: A Disorder of Fission of Organelles, Mitochondria, and Peroxisomes 546
Clinical Case Study 2: Paternal Inheritance of Mitochondrial DNA 546
Clinical Case Study 3: Treatment of Acetaminophen Toxicity with N-Acetylcysteine 547
Clinical Case Study 4: Alzheimer's Disease (AD) 547
Clinical Case Study 5: Methanol Toxicity 548
Clinical Case Study 6: Consequences of & #945
Clinical Case Study 7: Complement Deficiency 551
Clinical Case Study 8: Defects in Intracellular Killing by Phagocytes 551
Clinical Case Study 9: IgA Deficiency 552
Clinical Case Study 10: Impaired Development of T Cells and B Cells 552
Clinical Case Study 11: Biochemistry of Hemostasis 553
Clinical Case Study 12: Deficiency of Glycogenin-1 Leading to Glycogen Depletion in Skeletal Muscle Fibers and Cardiac Myocytes 556
Clinical Case Study 13: Acute Pancreatitis 557
Clinical Case Study 14: Precocious Puberty 557
Clinical Case Study 15: Lack of Physiologically Functioning Growth Hormone due to Disruption of the Intracellular Signalling Pathway 558
Clinical Case Study 16: Xeroderma Pigmentosum, a nucleotide Excision Repair Defect 559
Clinical Case Study 17: Disorders of Collagen Biosynthesis 559
Clinical Case Study 18: Use of Serum Electrophoretic and Related Studies for the Diagnosis of Multiple Myeloma and Small B-cell Neoplasms (Waldenström Macroglobulinemia) 560
Clinical Case Study 19: Celiac Disease 566
Clinical Case Study 20: A Neonatal Death due to Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency 567
Clinical Case Study 21: Acute Coronary Syndromes 568
Clinical Case Study 22: Hemoglobin Related Abnormalities 569
Clinical Case Study 23: Methemoglobinemia (MBMHb) 572
Clinical Case Study 24: Sn-Mesoporphyrin Therapy Instead of Exchange of Transfusion for Severe Neonate Hyperbilirubinemia (Neonatal Jaundice) 573
Clinical Case Study 25: L-Dihyroxy-Phenylalanine (L-DOPA, also known as Levodopa) Responsive Dystonia 574
Clinical Case Study 26: Hereditary Hemochromatosis (Chapter 27) 575
References for Additional Clinical Case Studies and Enrichment 575
Clinical Case Studies on Porphyrias 576
Clinical Case Studies and Supplemental Enrichment References for Electron Transport and Oxidative Phosphorylation: Chapter 13 576
Clinical Case Studies and Supplemental Enrichment References for Chapter 14 576
Clinical Case Study: A Defective Glucose-6-Phosphatase 576
Clinical Case Study: McArdle's Disease 576
Clinical Case Studies and Supplemental Enrichment References for Chapter 15 576
Clinical Case Studies and Supplemental Enrichment References for Chapter 19 577
Clinical Case Studies and Supplemental Enrichment References for Chapter 20 577
Clinical Case Study References for Activating (Gain-of-Function) Mutations of SUR1 and Kir6.2 Genes 577
Additional Clinical Case Studies on Diabetes Mellitus 577
Clinical Case Studies on Insulinoma Resulting in Hypoglycemia, a Diagnostically Challenging Problem 577
Clinical Case Studies on Obesity and Anorexia Nervosa (Chapter 20 Energy Homeostasis) 578
A Clinical Case Study on Anorexia Nervosa 578
Clinical Case Studies and Supplemental Enrichment References for Chapter 25: Nucleotide Metabolism 578
Clinical Case Studies and Supplemental Enrichment References on Signal Transduction (Chapter 23) 578
Clinical Case Studies and Supplemental Enrichment References on the Adrenal Glands (Chapter 30) 578
Clinical Case Study 2: Secondary Cushing's Syndrome Due to Metastatic Small-Cell Carcinoma of Prostatic Origin 579
Clinical Case Study 3: Adrenal Insufficiency 579
Clinical Case Study 4: 21-Hydroxylase Deficiency 579
Clinical Case Study 5: Pheochromocytoma 579
Clinical Case Studies and Supplemental Enrichment References on the Thyroid (Chapter 31) 579
Clinical Case Studies and Supplemental Enrichment References for Mineral Metabolism (Chapter 35) 579
Clinical Case Study for Copper Metabolism 580
Clinical Case Study for Zinc Deficiency 580
Clinical Case Studies and Supplemental Enrichment References for Vitamin Metabolism (Chapter 36) 580
Clinical Case Studies and Supplemental Enrichment References for Water, Electrolytes, and Acid-Base Balance (Chapter 37) 580
Appendix: Acronyms and Abbreviations Found in This Text 582
Index 588
A 588
B 589
C 589
D 591
E 591
F 592
G 592
H 593
I 594
J 594
K 594
L 595
M 595
N 596
O 596
P 596
Q 598
R 598
S 598
T 599
U 600
V 600
W 600
X 600
Z 600

Chapter 2. Water, Acids, Bases, and Buffers

Key Points

1. Water plays a major role in all aspects of metabolism and life is not possible without water.

2. Micelles are submicroscopic spherical aggregates of amphipathic molecules that contain large nonpolar hydrocarbon chains (hydrophobic groups) and polar or ionic groups (hydrophilic groups).

3. The reversible dissociation of water, although very weak, is important in maintaining and regulating the body's acid-base homeostasis.

4. An optimal acid-base balance is maintained in body fluids and cells despite large fluxes of metabolites. A buffer system protects the body from fluctuations in pH.

5. Metabolism produces both inorganic and organic acids. Acids generated from metabolites other than CO 2 are non-volatile and are excreted via the kidney. Non-volatile acids are lactic acid, acetoacetic acid, ?-hydroxybutyrate, and acids derived from sulfur-containing amino acids and phosphorous-containing compounds.

6. CO 2 produced by metabolism is transported as bicarbonate ion ( ) in the bicarbonate-carbonic system in plasma. CO 2 is eliminated in the lungs. Perturbations in this system can lead either to retention of CO 2 (acidosis) or to excessive loss of CO 2 (alkalosis).

7. Transport of CO 2 involves red blood cell carbonic anhydrase, which catalyzes the reversible reaction of hydration of CO 2 to H 2 CO 3 . Hemoglobin in tissue capillaries binds H + and releases oxygen to the tissues.

8. The H + ion concentration and the extracellular fluid, including plasma are maintained at pH 7.37 – 7.44 (36-43 nmol/L).

Properties of Water

Acid and base concentrations in living systems are carefully regulated to maintain conditions compatible with normal life. Biochemical reactions involving acids and bases occur in the body water, whereas buffer systems protect the body from significant variations in the concentrations of acids and bases. This chapter introduces basic concepts of the properties of water, acids, bases, and buffers.

Life cannot be sustained without water. Water constitutes 45–73% of total human body weight. It is distributed in intracellular (55%) and extracellular (45%) compartments and provides a continuous solvent phase between body compartments. As the biological solvent, water plays a major role in all aspects of metabolism: absorption, transport, digestion, and excretion of inorganic and organic substances, as well as maintenance of body temperature. The unique properties of water are due to its structure.

Hydrogen Bonding

Water (H 2 O) is a hydride of oxygen in which the highly electronegative oxygen atom attracts the bonding electrons from two hydrogen atoms. This leads to polar H—O bonds in which the hydrogen atoms have a slightly positive charge ( ? + ) and the oxygen atom has a slightly negative charge ? ? ) ( Figure 2-1 ). Water molecules have a relatively high dipole moment because of the angle (104 . 5°) of the H—O—H bond and the polarity of the bonds. Neighboring liquid water molecules interact with one another to form an extensive lattice-like structure, similar to the structure of ice. The intermolecular bonding between water molecules arises from the attraction between the partial negative charge on the oxygen atom and the partial positive charge on the hydrogen atom of adjacent water molecules. This type of attraction involving a hydrogen atom is known as a hydrogen bond ( Figure 2-2 ).

Figure 2-1

Structure of the water molecule.

Hydrogen bonds contain a hydrogen atom between two electronegative atoms (e.g., O and N). One is the formal hydrogen donor; the other is the hydrogen acceptor. The amount of energy required to break a hydrogen bond (bond energy) is estimated to be 2–5 kcal/mol (8.4–20.9 kJ/mol) in the gas phase. Covalent bonds have bond energies of 50–100 kcal/mol (209–418 kJ/mol). The cumulative effect of many hydrogen bonds is equivalent to the stabilizing effect of covalent bonds. In proteins, nucleic acids, and water, hydrogen bonds are essential to stabilize overall structure. In ice, each water molecule forms a hydrogen bond with four other water molecules, giving rise to a rigid tetrahedral arrangement ( Figure 2-2 ). In the liquid state, water maintains a tetrahedrally coordinated structure over short ranges and for short time periods.

Figure 2-2

Tetrahedral hydrogen-bonded structure of water molecules in ice. The tetrahedral arrangement is due to the fact that each water molecule has four fractional charges: two negative charges due to the presence of a lone pair of electrons on the oxygen atom and two positive charges, one on each of the two hydrogen atoms. In the liquid phase this tetrahedral array occurs transiently.

Physical Properties

Properties of water uniquely suited to biological systems include melting point, boiling point, heat of vaporization (quantity of heat energy required to transform 1 g of liquid to vapor at the boiling point), heat of fusion (quantity of heat energy required to convert 1 g of solid to liquid at the melting point), specific heat (the amount of heat required to raise the temperature of 1 g of substance by 1°C), and surface tension. All these values for water are much higher than those for other low molecular weight substances, because of the strong intermolecular hydrogen bonding of water. These properties contribute to maintenance of temperature and to dissipation of heat in living systems. Thus, water plays a major role in thermoregulation in living systems. The optimal body temperature is a balance between heat production and heat dissipation. Impaired thermoregulation causes either hypothermia or hyperthermia , and has serious metabolic consequences; if uncorrected, impaired thermoregulation may lead to death.

Water is transported across cell membranes in one of two ways: by simple diffusion through the phospholipid bilayer and by the action of membrane-spanning transport proteins known as aquaporins .

Thus, the concentration of water is in thermodynamic equilibrium across the cell membrane. In the renal collecting duct, water is reabsorbed through a specific aquaporin channel protein (aquaporin 2). This reabsorption of water is regulated by the antidiuretic hormone (also known as vasopressin ). A defect or lack of functional aquaporin 2, vasopressin, or its receptor leads to enormous loss of water in the urine, causing the disease known as diabetes insipidus ( Chapter 37 ). Water plays a significant role in enzyme functions, molecular assembly of macromolecules, and allosteric regulation of proteins. For example, the effect of protein solvation in allosteric regulation is implicated in the transition of deoxyhemoglobin to oxyhemoglobin. During this process about 60 extra water molecules bind to oxyhemoglobin.

Solutes, Micelles, and Hydrophobic Interactions

Water is an excellent solvent for both ionic compounds (e.g., NaCl) and low molecular weight nonionic polar compounds (e.g., sugars and alcohols). Ionic compounds are soluble because water can overcome the electrostatic attraction between ions through solvation of the ions. Nonionic polar compounds are soluble because water molecules can form hydrogen bonds to polar groups (e.g., –OH).

Amphipathic compounds , which contain both large nonpolar hydrocarbon chains (hydrophobic groups) and polar or ionic groups (hydrophilic groups) may associate with each other in submicroscopic aggregations called micelles . Micelles have hydrophilic (water-liking) groups on their exterior (bonding with solvent water), and hydrophobic (water-disliking) groups clustered in their interior. They occur in spherical, cylindrical, or ellipsoidal shapes. Micelle structures are stabilized by hydrogen bonding with water, by van der Waals attractive forces between hydrocarbon groups in the interior, and by energy of hydrophobic reactions. As with hydrogen bonds, each hydrophobic interaction is very weak, but many such interactions result in formation of large, stable structures.

Hydrophobic interaction plays a major role in maintaining the structure and function of cell membranes, the activity of proteins, the anesthetic action of nonpolar compounds such as chloroform and nitrous oxide, the absorption of digested fats, and the circulation of hydrophobic molecules in the interior of micelles in blood plasma.

Colligative Properties

The colligative properties of a solvent depend on the concentration of solute particles. These properties include freezing point depression, vapor pressure depression, osmotic pressure, and boiling point elevation. The freezing point of water is depressed by 1.86°C when 1 mol of nonvolatile solute, which neither dissociates nor associates in solution, is dissolved in 1 kg of water. The same concentration of solute elevates the boiling point by 0.543°C. Osmotic pressure is a measure of the tendency of water molecules to migrate from a dilute to a concentrated solution through a semipermeable membrane. This migration of water molecules is termed...

Erscheint lt. Verlag	28.1.2011
Sprache	englisch
Themenwelt	Sachbuch/Ratgeber
	Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
	Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
	Naturwissenschaften ► Biologie ► Biochemie
	Naturwissenschaften ► Chemie ► Organische Chemie
	Technik
ISBN-10	0-08-091688-0 / 0080916880
ISBN-13	978-0-08-091688-0 / 9780080916880

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