Medical Biochemistry

by Baynes, John W.; Dominiczak, Marek H.

• ISBN13: 9780723430124
• ISBN10: 0723430128
• Format: Paperback
• Copyright: 1999-09-01
• Publisher: Elsevier Science Health Science div

Summary

The experience of the editors reflects the book's aim: to present the core biochemical curriculum for medical students integrating clinical relevance throughout. The text has been focused through the selection and weighting of content while maintaining scientific rigour. Each chapter opener shows the overall metabolic chart highlighting the web of metabolic pathways allowing students to orientate themselves. Boxed clinical examples throughout the text take the science into a practical clinical context. Advanced concept boxes give students interested in a particular subject a further level of information. MCQs, patient-oriented problems and short answer questions at the end of each chapter enable the student to assess their understanding.

Author Biography

John W Baynes PhD: Carolina Distinguished Professor, Department of Chemistry and Biochemistry, and School of Medicine University of South Carolina, Columbia, South Carolina, USA Marek H Dominiczak MD FRCPath FRCP (Glasg) FACB: Consultant Chemical Pathologist, NHS Greater Glasgow, Western Infirmary and Gartnavel General Hospital; Honorary Clinical Senior Lecturer, University of Glasgow, UK; Docent in Laboratory Medicine, University of Turku, Finland

Table of Contents

Preface and User Guide	iii
Acknowledgements	iv
Contributors	v
Introduction
J Baynes
MH Dominiczak
The story of biochemistry - an overview	1	(4)
Amino Acids and Proteins
N Taniguchi
Introduction	5	(1)
Amino acids	5	(1)
Classification of amino acids based on chemical structure	6	(3)
Ionization state of an amino acid	9	(1)
Peptides and proteins	10	(5)
Purification and characterization of proteins	15	(6)
Blood and Transport Proteins
W Fraser
JC Chamberlain
Plasma and serum	21	(1)
Formed elements of blood	21	(1)
Plasma proteins	22	(4)
Immunoglobulins	26	(3)
The acute phase response	29	(2)
Oxygen Transport
G Helmkamp
Introduction	31	(1)
Properties of oxygen	31	(1)
General characteristics of mammalian globin proteins	32	(1)
Myoglobin: an oxygen-storage protein	33	(1)
Hemoglobin: an oxygen-transport protein	34	(1)
Transition between deoxygenated and oxygenated hemoglobin	35	(1)
Interactions with allosteric effectors	36	(2)
Normal hemoglobin variants	38	(1)
Sickle cell disease	38	(1)
Other hemoglobinopathies	39	(4)
Catalytic Proteins - Enzymes
J Fujii
Principles and classification of enzymes	43	(3)
Enzyme kinetics	46	(5)
Regulation of enzyme activity	51	(4)
Hemostasis and Thrombosis
G Lowe
Hemostasis	55	(2)
Vessel wall	57	(2)
Platelets	59	(2)
Coagulation	61	(4)
Fibrinolysis	65	(4)
Membranes and Transport
M Maeda
Membrane organization	69	(3)
Types of transport processes	72	(5)
Examples of transport systems and their coupling	77	(6)
Bioenergetics and Oxidative Metabolism
W Stillway
Oxidation as a source of energy	83	(1)
Free energy	84	(1)
Coupling with ATP	85	(1)
Mitochondrial synthesis of ATP from reduced coenzymes	86	(1)
The mitochondrial electron transport system	87	(5)
The ATP-synthetic proton gradient	92	(1)
Respiratory control	93	(1)
Inhibitors of oxidative metabolism	94	(3)
Function of the Gastrointestinal Tract in Digestionand Absorption of Fuels
J Broom
Introduction	97	(1)
General principles of digestion	98	(1)
Digestive enzymes and zymogens	99	(1)
Digestion and absorption of carbohydrate	99	(4)
Digestion and absorption of lipids	103	(2)
Digestion and absorption of proteins	105	(4)
Vitamins, Minerals and Nutrition
J Broom
Introduction	109	(1)
Recommended dietary allowances	109	(1)
Assessment of micronutrient status	110	(1)
Fat-soluble vitamins	110	(5)
Water-soluble vitamins	115	(6)
Trace metals	121	(4)
Anaerobic Metabolism of Glucose in the Red Cell
J Baynes
Introduction	125	(1)
Glycolysis	126	(4)
Regulation of glycolysis	130	(1)
Synthesis of 2,3-biphosphoglycerate	131	(1)
The pentose phosphate pathway	131	(1)
The redox stage of the pentose phophate pathway: synthesis of NADPH	132	(1)
The interconversion stage of the pentose phosphate pathway (Fig. 11.9)	132	(1)
Antioxidant defenses and reactive oxygen species	133	(1)
The beneficial effects of reactive oxygen	134	(2)
The glyoxalase pathway: a special role for glutathione	136	(3)
Carbohydrate Storage and Synthesis in Liver and Muscle
J Baynes
Introduction	139	(1)
Structure of glycogen	140	(1)
Pathway of glycogenesis from blood glucose in liver	140	(1)
Pathway of glycogenolysis in liver	141	(1)
Hormonal regulation of hepatic glycogenolysis	142	(1)
Mechanism of action of glucagon	143	(3)
Mobilization of hepatic glycogen by epinephrine	146	(2)
Glycogenolysis in muscle	148	(1)
Regulation of glycogenesis	149	(2)
Gluconeogenesis	151	(6)
The Tricarboxylic Acid Cycle
W Stillway
Introduction	157	(1)
Energy production	157	(3)
Pyruvate carboxylase	160	(2)
The pyruvate dehydrogenase complex	162	(1)
Enzymes and reactions of the tricarboxylic acid cycle	163	(2)
Energy yield from the tricarboxylic acid cycle	165	(1)
Regulation of the tricarboxylic acid cycle	165	(2)
Anaplerotic reactions	167	(2)
Oxidative Metabolism of Lipids in Liver and Muscle
J Baynes
Activation of fatty acids and their transport to the mitochondrion	169	(2)
Oxidation of fatty acids	171	(2)
Ketogenesis in liver	173	(6)
Biosynthesis and Storage of Fatty Acids in Liver and Adipose Tissue
J Broom
Fatty acid synthesis	179	(4)
Fatty acid elongation	183	(1)
Desaturation of fatty acids	184	(1)
Storage and transport of fatty acids: the synthesis of triacylglycerols (triglycerides)	185	(1)
Regulation of total body fat stores	186	(3)
Biosynthesis of Cholesterol in Liver
G Beastall
Structure of cholesterol	189	(1)
Biosynthesis of cholesterol	190	(4)
Role of cholesterol	194	(1)
Bile acids	194	(2)
Steroid hormones	196	(2)
Vitamin D3	198	(1)
Cholesterol metabolism and excretion	199	(2)
Lipids and Lipoproteins
MH Dominiczak
Lipoproteins	201	(1)
The transport of fatty acids and triglycerides between tissues	201	(1)
Cholesterol: a structural component and a steroid hormone precursor	201	(1)
Plasma lipoproteins	202	(1)
Apoproteins (apolipoproteins)	203	(1)
The apoprotein content of lipoprotein classes	203	(1)
Lipoprotein metabolism enzymes and transfer proteins	204	(1)
Lipoprotein (a)	204	(1)
Measurement of lipoproteins	205	(1)
Lipoprotein metabolism	206	(1)
The transport of dietary fat	207	(1)
Transport of endogenously synthesized lipids	207	(2)
Cholesterol removal from cells (reverse cholesterol transport)	209	(1)
The concept of two main pathways of lipoprotein metabolism	209	(1)
Lipoprotein receptors	209	(2)
Atherogenesis	211	(2)
The assessment of cardiovascular risk	213	(4)
Biosynthesis and Degradation of Amino Acids
A Rawitch
Amino acid metabolism - overview	217	(1)
Nitrogen metabolism	217	(8)
Metabolism of the carbon skeletons of amino acids	225	(3)
Amino acid biosynthesis	228	(1)
Inherited diseases of amino acid metabolism	228	(3)
Signaling molecules	231	(2)
Muscle: Energy Metabolism and Contraction
J Baynes
Introduction	233	(1)
Structure of muscle	233	(2)
Muscle proteins	235	(2)
The contractile response	237	(1)
Cardiac and smooth muscle	237	(1)
Muscle energy metabolism	238	(5)
Glucose Homeostasis and Fuel Metabolism
MH Dominiczak
The metabolic fuels	243	(1)
The organ-fuel interactions	244	(1)
Glucose homeostasis	244	(4)
Fine-tuning of fuel metabolism	248	(2)
Hypoglycemia	250	(1)
The assessment of fuel metabolism status	251	(2)
Metabolism after a meal and in the fasting state (terminology)	253	(1)
Postprandial (absorptive) state	253	(1)
Postabsorptive state	254	(2)
Prolonged fast and starvation	256	(1)
Stress and metabolic response to injury	257	(2)
Diabetes mellitus: a disorder of fuel metabolism	259	(8)
Water and Electrolyte Balance: Kidney Function
M Szczepanska-Konkel
G Beastall
MH Dominiczak
Body water	267	(2)
Osmolality and volume of body fluids	269	(2)
The water balance	271	(1)
The kidney	271	(4)
The renin-angiotensin system	275	(2)
Water metabolism and sodium metabolism are closely interrelated	277	(1)
Renal clearance and glomerular filtration rate	277	(2)
The importance of plasma potassium concentration	279	(1)
Antidiuretic hormone (ADH) and the renin-angiotensin system in water and electrolyte disorders	279	(4)
Lung and Kidney: The Control of Acid--Base Balance
MH Dominiczak
M Szczepanska-Konkel
The acid-base balance	283	(1)
The body buffer systems	283	(3)
Blood gas measurement	286	(1)
The lung	287	(2)
The handling of carbon dioxide	289	(1)
The kidney	290	(1)
The metabolic and respiratory acid--base disorders	291	(4)
Calcium and Bone Metabolism
W Fraser
Cellular activity within bone	295	(2)
Calcium metabolism	297	(2)
Factors influencing calcium homeostasis	299	(1)
Calcium absorption and excretion	300	(1)
Muscle energy metabolism	301	(1)
Disorders of calcium metabolism: hypercalcemia	302	(1)
Disorders of calcium metabolism: hypocalcemia	303	(2)
Metabolic bone disease	305	(3)
Complex Carbohydrates: Glycoproteins
A Elbein
Structures and linkages	308	(2)
Interconversions of dietary sugars	310	(3)
Other pathways of sugar nucleotide metabolism	313	(1)
Biosynthesis of oligosaccharides	314	(3)
Functions of the oligosaccharide chains of glycoproteins	317	(4)
Complex Lipids
A Elbein
Glycerophospholipids (phospholipids)	321	(1)
Biosynthesis of precursors: phosphatidic acid and diacyl glycerol	322	(2)
Biosynthesis of phospholipids	324	(2)
Plasmalogens	326	(1)
Sphingolipids	327	(1)
Sphingomyelin	327	(1)
Glycolipids	327	(6)
The Extracellular Matrix
A Elbein
GP Kaushal
Collagen	333	(2)
Synthesis and post-translational modification of collagens	335	(1)
Noncollagenous proteins in the extracellular matrix	336	(1)
Elastin	336	(2)
Fibronectin	338	(1)
Laminins	339	(1)
Proteoglycans	339	(7)
Special Liver Function
A F Jones
The structure of the liver	346	(1)
Heme synthesis	347	(1)
Bile acid metabolism	348	(1)
Ammonia	349	(1)
Liver turnover of proteins	350	(1)
Drug metabolism	350	(1)
Drug hepatotoxicity	351	(1)
Biochemical tests of liver function	352	(1)
Classification of liver disorders	353	(3)
Genetic causes of jaundice	356	(1)
Biosynthesis and Degradation of Nucleotides
R Thornburg
Overview of nucleotide metabolism	357	(1)
De novo synthesis of inosine monophosphate	358	(2)
Pyrimidine metabolism	360	(3)
Pyrimidine-salvage pathways	363	(1)
Formation of deoxynucleotides	364	(3)
Deoxyribonucleic Acid
R Thornburg
Structure of deoxyribonucleic acid (DNA)	367	(5)
The cell cycle	372	(2)
Oxidative damage to DNA	374	(6)
Ribonucleic Acid
G Bannon
The molecular anatomy of RNA molecules	380	(1)
RNA polymerases	381	(2)
The process of transcription	383	(2)
Post-transcriptional processing	385	(4)
Protein Synthesis
G Bannon
The genetic code	389	(2)
The machinery of protein synthesis	391	(3)
The process of protein synthesis	394	(3)
Protein targeting and post-translational modifications	397	(4)
Control of Gene Expression
A Jamieson
The basic mechanisms of gene expression	401	(4)
Steroid receptors	405	(2)
Organization of the steroid receptor molecule	407	(1)
Alternative approaches to gene regulation in humans	408	(1)
Gene expression	408	(5)
Recombinant DNA Technology
A Jamieson
Introduction	413	(1)
Hybridization	413	(3)
Methods used in labelling nucleotide proteins	416	(1)
DNA storage	417	(2)
DNA amplification and cloning	419	(1)
Cell-based cloning	420	(3)
Polymerase chain reaction-based DNA cloning	423	(2)
Specific methods used in the analysis of DNA	425	(2)
PCR-based methods	427	(3)
Other methods for detection of variation in DNA	430	(2)
DNA sequencing	432	(3)
The Immune Response
A Farrell
Introduction	435	(1)
The nonspecific immune response	435	(2)
The specific immune response	437	(1)
Lymphoid tissues	437	(1)
Lymphocyte circulation	438	(1)
Lymphocytes	439	(1)
Molecules involved in antigen recognition	439	(2)
The reaction with, response to, and elimination of antigen	441	(2)
Major histocompatibility complex	443	(1)
MHC expression patterns and restriction	444	(1)
Humoral-mediated specific immune response	444	(3)
The cellular and molecular elements of the integrated immune response	447	(1)
Immunologic dysfunction	447	(4)
Biochemical Endocrinology
G Beastall
The endocrine system	451	(2)
The hypothalamo--pituitary regulatory system	453	(1)
The hypothalamo--pituitary--thyroid axis	454	(3)
The hypothalamo--pituitary--adrenal axis	457	(2)
The hypothalamo--pituitary--gonadal axis	459	(5)
The growth hormone axis	464	(2)
The prolactin axis	466	(4)
Membrane Receptors and Signal Transduction
M Harnett
Cell-surface membrane receptors	470	(1)
Steroid hormones	470	(2)
Polypeptide hormones	472	(1)
G-protein-coupled receptors: the β-adrenergic receptor	473	(3)
Second messengers	476	(1)
Cyclic AMP	476	(1)
Calcium ion as an intracellular messenger	476	(3)
Second messenger role for inositol biphosphate	479	(1)
Diacyl glycerol as second messenger	480	(2)
Phospholipase A2 and arachidonic acid messenger	482	(5)
Neurochemistry
E Thompson
Brain and peripheral nerve	487	(2)
The different cells of the nervous system	489	(1)
Neurons	490	(1)
Neurological structures	491	(1)
Synaptic transmission	491	(1)
Types of synapse	492	(1)
Cholinergic transmission	492	(1)
Adrenergic transmission	492	(1)
Ion channels	492	(2)
The mechanism of vision	494	(3)
Neurotransmitters
D Shapiro
Neurotransmitters	497	(1)
Neurotransmission	498	(3)
The various classes of neurotransmitters	501	(2)
Catecholamines	503	(4)
Acetycholine	507	(4)
Cell Growth, Differentiation, and Cancer
M Harnett
The cell cycle	511	(1)
Growth factors	512	(7)
Apoptosis	519	(2)
Cancer	521	(6)
Appendix: the overview chart	527	(24)
Questions and Answers
Multiple choice questions	528	(7)
Patient oriented problems	535	(4)
Short answer questions	539	(3)
MCQ answers	542	(1)
Patient oriented answers	543	(2)
Short answers	545	(6)
Abbreviations	551	(3)
Index	554