1.4.5 Mitochondria are the energy factories of the cell. 1.4.6 Lysosomes function in intracellular digestion. 1.4.7 Peroxisomes contain oxidative enzymes and metabolize hydrogen peroxide. 1.4.8 The cytoskeleton organizes the cells contents. 1.4.9 The cytosol contains soluble components, is gel-like, and also has loser organization. 1.5 The cell is a complex organization where both structure and function are important.
Clinical Correlations cc 1.1 Blood Bicarbonate Concentration in Metabolic Acidosis cc 1.2 Mitochondrial Diseases cc 1.3 Lysosomal Enzymes and Gout cc 1.4 Lysosomal Acid Lipase Deficiency cc 1.5 Zellweger Syndrome and the Absence of Functional Peroxisomes
2.3.6 At the pI the molecule doesnt move. 2.3.7 Amino acid R-groups can be polar or nonpolar. 2.3.8 Amino acids are chemically reactive. 2.4 Primary Structure of Proteins 2.4.1 Insulin is an illustration. 2.5 Higher Levels of Protein Organization 2.5.1 Proteins have secondary structure. 2.5.1.1 Coiled _-helical structure. 2.5.1.2 Flat _-sheets. 2.5.1.3 Additional organization features. 2.5.2 Proteins fold into a 3-D tertiary structure. 2.5.3 There can be families of proteins with common structural parameters. 2.5.4 When multiple protein chains interact there is quaternary structure. 2.6 Other Types of Proteins
2.6.1 Examples of fibrous proteins are collagen, elastin, _-keratin, and tropomysin. 2.6.1.1 Collagen is found in all human tissues and organs. 2.6.1.2 Table 2.10 shows the amino acid composition of collagen. 2.6.1.3 Collagen has long stretches where glycine occurs every third residue. 2.2.1.4 A diagram of collagen is in Figure 2.38. 2.6.1.5 There are covalent cross-links in collagen. 2.6.1.6 Elastin has allysine-generated cross-links. 2.6.2 Lipoproteins are comlexes of lipids and proteins. 2.6.3 Glycoproteins contain carbohydrates and protein. 2.7 Folding of Proteins from Randomized to Unique Structures: Protein Stability 2.7.1 A possible pathway for protein folding pathway is presented. This is currently a very active research area. 2.7.2 Chaperone proteins assist in the folding process. 2.7.3 Noncovalent forces aid in folding and stability. 2.7.4 Denaturation of proteins leads to a loss of structure. 2.8 Dynamic Aspects of Protein Structure 2.8.1 Proteins are constantly in motion and are not in the static structure revealed by x-ray crystallography. 2.9 Methods for Characterization, Purification, and Study of Protein Structure and Organization 2.9.1 Proteins can be separated on the basis of charge. 2.9.2 Proteins can be separated on the basis of mass or size. 2.9.3 Proteins can be separated on the basis of chemical properties. 2.9.4 The amino acid sequence of a protein can be determined. 2.9.5 The 3-D structures of proteins can be determined by x-ray crystallograpphic methods. 2.9.6 Proteins can be characterized spectroscopically.
Clinical Correlations cc 2.1 Plasma Proteins in Diagnosis of Disease cc 2.2 Differences in Primary Structure of Insulins Used in Treatment of Diabetes Mellitus cc 2.3 A Nonconservative Mutation Occurs in Sickle Cell Anemia cc 2.4 Symptoms of Diseases of Abnormal Collagen Synthesis cc 2.5 Hyperlipidemias cc 2.6 Hypolipoproteinemias cc 2.7 Glycosylated Hemoglobin, HbA1c cc 2.8 Use of Amino Acid Analysis in Diagnosis of Disease
Clinical Correlations cc 3.1 The Complement Proteins cc 3.2 Functions of Different Antibody Classes cc 3.3 Immunization cc 3.4 Fibrin Formation in a Myocardial Infarct and the Action of Recombinant Tissue Plasminogen Activator (rtPA) cc 3.5 Involvement of Serine Proteases in Tumor Cell Metastasis
4.4.4 FMN and FAD are hydrogen-carrying coenzymes derived from riboflavin. 4.4.5 Metal ions can serve various functions as cofactors. 4.4.5.1 Metals can have a structural role. 4.4.5.2 Metals can function in redox reactions. 4.5 Inhibition of Enzymes 4.5.1 Competitive inhibitors can be reversed by increased [substrate]. 4.5.2 Noncompetitve inhibitors do not prevent substrate binding. 4.5.3 Reversible inhibition leads to covalent modification of an enzyme. 4.5.3.1 Many drugs inhibit enzyme action. 4.5.3.1.1 Sulfa drugs compete with PABA. 4.5.3.1.2 Methotrexate competes with folates. 4.5.3.1.3 Nonclassical inhibitors that upon an enzymes action become a highly reactive species. 4.5.3.1.4 Fluorouracil and 6-mercaptopurine are other significant purine/pyrimidine inhibitors 4.6 Allosteric Control of Enzyme Activity 4.6.1 Allosteric inhibitors bind at sites different from substrate binding sites. 4.6.2 Allosteric enzymes exhibit sigmodial kinetics. 4.6.3 Cooperativity explains interaction between ligand sites in an oligomer protein. 4.6.4 Regulatory subunits modulate the activity of catalytic subunits. 4.7 Enzyme Specificity: The Active Site 4.7.1 Complementarity of substrate and enzyme explains substrate secificity., 4.7.2 Not all enzymes can distinguish between two isomers. 4.8 Mechanism of Catalysis 4.8.1 Enzymes decrease activation energy. 4.8.1.1 Acid-base mechanisms can be used catalytically. 4.8.1.2 Strain in the substrate can be introduced. 4.8.1.3 Covalent bonds are sometimes formed during catalysis. 4.8.1.4 Transition states can be stabilized. 4.8.1.5 A decrease in entropy can function in catalysis. 4.8.2 Abzymes are artificially synthesized antibodies with catalytic activity. 4.8.3 Enviornmental factor can influence catalysis. 4.8.3.1 Temperature 4.8.3.2 pH 4.9 Clinical Applications of Enzymes 4.9.1 Coupled assays often involve changes that be monitored spectrophotometrically. 4.9.2 Clinical analyzers use immobilized enzymes as reagents. 4.9.3 Enyme-linked immunoassays employ enzymes as indicators. 4.9.4 Isozymes are diagnostically important. 4.9.5 Some enzymes can be used as therapeutic agents.. 4.9.6 Enzymes linked to insoluble matrices are used as chemical reactors. 4.10 Regulation of Enzyme Activity
Clinical Correlations
cc 4.1 A Case of Gout Demonstrates Two Phases in the Mechanism of Enzyme Action cc 4.2 The Physiological Effect of Changes in Enzyme Km Value cc 4.3 Mutation of a Coenzyme Binding Site Results in Clinical Disease cc 4.4 A Case of Gout Demonstrates the Difference Between an Allosteric and the SubstrateBinding Site cc 4.5 Thermal Lability of Glucose 6 Phosphate Dehydrogenase Results in Hemolytic Anemia cc 4.6 Alcohol Dehydrogenase Isoenzymes with Different pH Optima cc 4.7 Identification and Treatment of an Enzyme Deficiency cc 4.8 Ambiguity in the Assay of Mutated Enzymes
5.5.5.1 Passive 5.5.5.2 Active 5.6 Channels and Pores 5.6.1 Channels and pores in membranes function differently. 5.6.2 Opening and closing of channels are controlled. 5.6.2.1 Sodium channel 5.6.2.2 Nicotinic-acetylcholine channel 5.6.3 Examples of pores are gap functions and nuclear pores. 5.7 Passive Mediated Transport Systems 5.7.1 Glucose transport is facilitated. 5.7.2 Cl- and HCO3- are transported by an antiport mechanism. 5.7.3 Mitochondria contain a number of transport systems. 5.8 Active Mediated Transport Systems 5.8.1 Translocation of Na+ and K+ is a primary active transport system. 5.8.2 All plasma membranes contain a Na+,K+-activated ATPase. 5.8.3 Erythrocyte ghosts are used to study Na+,K+ -activated translocation. 5.8.4 Ca2+ translocation is another example of a primary active transport system. 5.8.5 Na+-dependent transport of glucose and amino acids are secondary active transport systems. 5.8.6 Group translocation involves chemical modification of the substrate transported. 5.8.7 Summary of transport systems. 5.9 Ionophores
Clinical Correlations cc 5.1 Liposomes as Carriers of Drugs and Enzymes cc 5.2 Abnormalities of Cell Membrane Fluidity in Disease States cc 5.3 Cystic Fibrosis and the Cl- Channel cc 5.4 Diseases Due to Loss of Membrane Transport Systems
6.3.2 Pyruvate dehydrogenase is a multienzyme complex. 6.3.3 Pyruvate dehydrogenase is strictly regulated. 6.3.3.1 In bacteria the pryvuate dehydrogenase complex is regulated by products and substrates. 6.3.3.2 In animals there is a covalent modification/demodification. 6.3.4 Acetyl CoA is used by several different pathways. 6.4 The Tricarboxylic Acid Cycle 6.4.1 The reactions of the tricarboxylic acid cycle are shown in Fig. 6.19. 6.4.2 Conversion of the acetyl group of acetyl CoA to CO2 and H2O conserves energy. 6.4.3 The activity of the tricarboxylic acid cycle is crefully regulated. 6.5 Structure and Compartmentation of the Mitochondrial Membranes 6.5.1 Inner and outer mitochondrial membranes have different compositions and functions. 6.5.2 Mitochondrial inner membranes contain substrate transport systems. 6.5.3 Substrate shuttles transport reducing equivalents across the inner mitochondrial membrane. 6.5.4 Acetyl units are transported by citrate. 6.5.5 Transport of adenine nucleotides and phosphate 6.5.5.1 There is an adenine nucleotide translocator. 6.5.5.2 Phosphate is transport by an exchanger. 6.5.6 Mitochondria have a specific calcium transport mechanism. 6.6 Electron Transfer 6.6.1 Redox reactions 6.6.2 Free-energy changes in redox reactions. 6.6.3 Mitochondrial electron transport is a multicomponent system. 6.6.3.1 NAD-linked dehydrogenase 6.6.3.2 Flavin-linked dehydrogenase 6.6.3.3 Iron-sulfur centers 6.6.3.4 Cytochromes 6.6.3.5 Coenzyme Q 6.6.4 The mitochondrial ele4ctron transport chain is located in the inner membrane in a specific sequence. 6.6.5 Electron transport can be inhibited at specific sites. 6.6.6 Electron transport is reversible. 6.6.7 Oxidative phosphorylation is coupled to electron transport. 6.7 Oxidative Phosphorylation 6.7.1 The chemiosmotic-coupling mechanism involves the generation of a proton gradient and reversal of an ATP-dependent proton pump.
Clinical Correlations
cc 6.1 Pyruvate Dehydrogenase Deficiency cc 6.2 Fumarase Deficiency cc 6.3 Mitochondrial Myopathies cc 6.4 Subacute Necrotizing Encephalopathy cc 6.5 Cyanide Poisoning
7.4.3.5 6-Phosphofructo-2-kinase and fructose 2,6-bisphosphase are domains of a bifunctional polypeptide regulated by phosphorylation/dephosphorylation.. See Fig 7.23. 7.4.3.6 The heart contains a different isozyme of the bifunctional enzyme. 7.4.4 Pyruvate kinase is a regulated enzyme of glycolysis. 7.5 Gluconeogenesis 7.5.1 Glucose is required for survival. 7.5.2 The Cori and alanine cycles are paths for lactate and alanine return to the liver for gluconeogenesis. 7.5.3 Pathway of glucose synthesis from lactate includes lactic dehydrogenase and pyruvate kinase and requires 6 ATPs. 7.5.4 Pyruvate carboxylase and phosphoenolpyruvate carboxykinase also function in gluconeogeneis. 7.5.5 Gluconeogenesis uses many glycolytic enzymes but in the reverse direction. 7.5.6 Glucose can from synthesized from the carbon chains of glucogenic amino acids (all except leucine and lysine). 7.5.7 Glucose can be synthesized from odd-chain fatty acids via propionyl CoA. 7.5.8 Glucose can be synthesized from other sugars. 7.5.8.1 Fructose 7.5.8.2 Galactose 7.5.8.3 Mannose 7.5.9 Gluconeogenesis requires expenditure of 6 ATPs per glucose formed. 7.5.10 Gluconeogenesis is regulated at the glucose 6-phosphatase, phosphofructokinase, and pyvuate carboxylase steps. These are catalyzed by enzymes that arent a part of glycolysis. 7.5.11 Glucagon and insulin are hormones that regulate the balance of gluconeogenesis and glycolysis. 7.5.12 Ethanol ingestion inhibits gluconeogenesis. 7.6 Glycogenolysis and Glycogenesis 7.6.1 Glycogen, a storage form of glucose, serves as a ready source of energy. 7.6.2 Glycogen phosphorylase catalyzed the removal of one glucose unit as glucose 1-phosphate from glycogen. 7.6.2 The debranching enzyme is required for complete hydrolysis of glycogen. 7.6.3 Synthesis of glycogen requires unique enzymes. 4.5.3.1 Glycogen synthase 7.6.4 There are special features of glycogen degradation and synthesis. 7.6.4.1 We store glycogen because it is a good fuel reserve. 4.5.3.2 Glycogenin, a protein, is required as a primer for glycogen synthesis. 4.5.3.3 Glycogen limits its own synthesis. 4.5.4 Glycogen synthesis and degradation are highly regulated processes. 4.5.4.1 Regulation of glycogen phosphorylase. See Fig. 7.57.
4.5.4.2 The cascade that regulates glycogen phosphorylase amplifies a small signal into a very large effect. 4.5.4.3 Regulation of glycogen synthase is shown in Fig. 7.58. 4.5.4.4 Regulation of phosphoprotein phosphatases which functions for the removal of phosphates from proteins is part of the scheme. 4.5.5 Effector control of glycogen metabolism 4.5.5.1 There is negative feedback control by glycogen. 4.5.5.2 Phosphorylase functions as a glucose receptor in liver. 4.5.5.3 Glucagon stimulates glycogen degradation in the liver. 4.5.5.4 Epinephrine stimulates glycogen degradation in the liver. 4.5.5.5 Epinephrine stimulates glycogen degradtion in heart and skeletal muscle. 4.5.5.6 There is neural control of glycogen degradation in skeletal muscle. 4.5.5.7 Insulin stimulates glycogen synthesis in muscle and liver.
Clinical Correlations cc 7.1 Alcohol and Barbiturates cc 7.2 Arsenic Poisoning cc 7.3 Fructose Intolerance cc 7.4 Diabetes Mellitus cc 7.5 Lactic Acidosis cc 7.6 Pickled Pigs and Malignant Hyperthermia cc 7.7 Angina Pectoris and Myocardial Infarction cc 7.8 Pyruvate Kinase Deficiency and Hemolytic Anemia cc 7.9 Hypoglycemia and Premature Infants cc 7.10 Hypoglycemia and Alcohol Intoxication cc 7.11 Glycogen Storage Diseases
8.3.1 Isomerization and phoshporylation are common reactions for interconverting carbohydrates. 8.3.2 Nucleotide-linked sugars are intermediates in many sugar transformations. 8.3.3 Epimerization interconverts glucose and galactose. 8.3.4 Glucuronic acid is formed by oxidation of UDP-glucose. 8.3.5 Decarboxylation, oxidoreduiction, and transamination of sugars produce necessary produts. 8.3.6 Sialic acids are derived from N-acetylglucosamine. 8.4 Biosynthesis of Complex Carbohydrates 8.4.1 Glucosyltransferases specifically transfer to other carbohydrate containing molecules. 8.5 Glycoproteins 8.5.1 Glycoproteins contain variable amount of carbohydrate. 8.5.2 Carbohydrates are covalently linked to glycoproteins by N- or Oglycosyl bonds. 8.5.3 Synthesis of N-linked glycoproteins involves dolichol phosphate. 8.6 Proteoglycans 8.6.1 Hyaluronate is a copolymer of N-acetylglucosamine and glucuronic acid. 8.6.2 Chondroitin sulfates are the most abundant glycosaminoglycans. 8.6.3 Dermatan sulfate contains L-iduronic acid. 8.6.4 Heparin and heparan sulfate differ from other glycosaminoglycans 8.6.5 Kertan sulfate exists in two forms. 8.6.6 The biosynthesis of chondroitin sulfate is typical of glycosaminoglycan formatin.
Clinical Correlations cc 8.1 Glucose 6 Phosphate Dehydrogenase: Genetic Deficiency or Presence of Genetic Variants inErythrocytes cc 8.2 Essential Fructosuria and Fructose Intolerance: Deficiency of Fructokinase and Fructose 1 PhosphateAldolase cc 8.3 Galactosemia: Inability to Transform Galactose into Glucose cc 8.4 Pentosuria: Deficiency of Xylitol Dehydrogenase cc 8.5 Glucuronic Acid: Physiological Significance of Glucuronide Formation cc 8.6 Blood Group Substances cc 8.7 Aspartylglycosylaminuria: Absence of 4 L Aspartylglycosamine Amidohydrolase cc 8.8 Heparin Is an Anticoagulant cc 8.9 Mucopolysaccharidoses
9.2.2 Nomenclature of fatty acids. See Table 9.1. 9.2.3 Most fatty acids in humans occur as traiacylglycerols. 9.2.4 The hydrophobic nature of lipids is important to their biological function. 9.3 Sources of Fatty Acids 9.3.1 Most fatty acids are supplied in the diet. 9.3.2 Palmitate can be synthesized from acetylCoA. 9.3.3 Formation of malonyl CoA is the commitment step of fatty acid synthesis. 9.3.4 The reaction sequence of fatty acid synthesis is shown in Fig. 9.7. 9.3.5 Mammalian fatty acid synthase is a multifunctional polypeptide. 9.3.6 Stoichiometry 8 acetyl CoAs, 7 ATPs, 14 NADPHs, and 14 protons are used to make palmitate. 9.3.7 Acetyl CoA must be transported from mitochondria to the cytosol for palmitate synthesis. 9.3.8 Palmitate is the precursor of other fatty acids. 9.3.8.1 Elongation reactions add carbons. 9.3.8.2 Desaturation reactions removed hydrogens. 9.3.8.3 A series of reactions is involved in the synthesis and modification of polyunsaturated fatty acids. 9.3.8.4 Hydroxy fatty acids are formed in nerve tissue. 9.3.9 Fatty acid synthesis can produce fatty acids other than palmitate. 9.3.10 Fatty acyl CoAs may be reduced to fatty alcohols. 9.4 Storage of Fatty Acids as Triacylglycerols 9.4.1 Triacylglycerols are synthesized from fatty acyl ColAs and glycerol 3-phsphate in most tissues. 9.4.2 Mobilization of triacylglycerols requires hydrolysis. 9.5 Methods of Interorgan Transport of Fatty Acids and Their Primary Products 9.5.1 Lipid-based energy is transported in the blood in different forms. 9.5.1.1 Plasma lipoproteins can tracylglycerols and other lipids. 9.5.1.2 Fatty acids can be bound to serum albumin. 9.5.1.3 Ketone bodies are a lipid-based energy source used in starvation. 9.5.2 Lipases must hydrolyze blood triacylglycerols for their fatty acids to become available to tissues. 9.6 Utilization of Fatty Acids for Energy Production 9.6.1 -Oxidation of straight-chain fatty acids is the major energy-producing process. 9.6.1.1 Fatty acids are activated by conversion to fatty acyl CoA. 9.6.1.2 Carnitine carries acyl groups across the mitochondrial membrane. 9.6.1.3 -Oxidation is a sequence of four reactions. 9.6.2 Comparison of the b-oxidation scheme with palmitate biosynthesis. See table 9.4. 9.6.3 Some fatty acids require modification of -oxidation for metabolism. 9.6.3.1 Proprionyl CoA is produced by oxidation of odd-chain fatty acids. 9.6.3.2 Oxidation of unsaturated fatty acids requires additional enzymes. 9.6.3.3 Some fatty acids undergo -oxidation.
9.6.3.4 -Oxidation gives rise to a dicarboxylic acid. 9.6.4 Ketone bodies are formed from acetyl CoA. 9.6.4.1 HMG CoA is an intermediate in the synthesis of acetoacetate from acetyl CoA. 9.6.4.2 Acetoacetate forms both D--hydroxybutyrate and acetone. 9.6.4.3 Utilization of ketone bodies by nonhepatic tissues requires formation of acetoacetyl CoA. 9.6.4.4 Starvation and certain pathological conditions lead to ketosis. 9.6.5 Peroxisomal oxidation of fatty acids serves many functions.
Clinical Correlations cc 9.1 Obesity cc 9.2 Leptin and Obesity cc 9.3 Genetic Abnormalities in Lipid Energy Transport cc 9.4 Genetic Deficiencies in Carnitine or Carnitine Palmitoyl Transferase cc 9.5 Genetic Deficiencies in the Acyl CoA Dehydrogenases cc 9.6 Refsum's Disease cc 9.7 Diabetic Ketoacidosis
10.3.3 Cholesterol is synthesized from acetyl CoA. 10.3.3.1 Mevalonic acid is a key intermediate. 10.3.3.2 Mevalonic acid is a precursor of farnesyl pyrophosphate. 10.3.3.3 Cholesterol is formed from farnesyl pyrophosphate via squalene. 10.3.4 Cholesterol biosynthesis is carefully regulated. 10.3.5 Plasma cholesterol is in a dynamic state. 10.3.6 Cholesterol is excreted primarily as bile acids. 10.3.7 Vitamin D is synthesized from an intermediate of cholesterol biosynthesis dehydrocholesterol. 10.4 Sphingolipids 10.4.1 Biosynthesis of sphingosine 10.4.2 Ceramides are fatty acid amide derivatives of sphingosine. 10.4.3 Sphingomyelin is the only sphingolipid containing phosphorus. 10.4.3.1 Sphingomyelin is synthesized from a ceramide and phosphatidylcholine. 10.4.4 Glycosphingolipids usually have a galactose or glucose unit. 10.4.4.1 Cerebrosides are glycosylceramides. 10.4.4.2 Sulfatide is a sulfuric acid ester of galactocerebroside. 10.4.4.3 Globosides are ceramide oligosacchrides. 10.4.4.4 Gangliosides contain sialic acid. 10.4.5 Sphingolipidoses are lysomal storage disease with defect in the catabolic pathway for sphingolipids. 10.4.5.1 Diagnostic enzyme assays for sphingolipidoses. 10.5 Prostaglandins and Thromboxanes 10.5.1 Prostaglandins and thromboxanes are derivatives of twenty-carbon, monocarboxylic acids. 10.5.2 Synthesis of prostaglandins involvess a cyclooxygenase. ` 10.5.2.1 Prostaglandin production is inhibited by steroidal and nonsteroidal anti-inflammatory agents. 10.5.3 Prostaglandins exhibit many physiological effects. 10.6 Lipoxygenase and Oxyeicosatetraenoic Acids 10.6.1 Monohydroperoxyeicostetraenoic acids are produts of lipoxygenase action. 10.6.2 Leukotrienes and hydroxyeicostertraenoic acids are hormones derived from HPETEs. 10.6.3 Leukotrienes and HETEs affect several physiological processes.
Clinical Correlations cc 10.1 Respiratory Distress Syndrome cc 10.2 Treatment of Hypercholesterolemia cc 10.3 Atherosclerosis cc 10.4 Diagnosis of Gaucher's Disease in an Adult
11.1 Human have forgotten how to synthesize 10 different amino acids. These must be supplied in the diet. They are listed in Table 11.2 Incorporation of Nitrogen into Amino Acids 11.2.1 Most amino acids are obtained from the diet. It is cheaper to import than manufacture. 11.2.2 Amino groups are transferred between different amino acids using keto acid intermediates and vitamin B6 coenzymes. 11.2.3 Pyridoxal phosphate is the cofactor for aminotransferases. 11.2.4 Glutamte dehydrogenase incorporates and produces ammonia. 11.2.5 Free ammonia is incorporated into and produced from glutamine. 11.2.6 The amide group of asparagine is derived from glutamine. 11.2.7 Amino acid oxidases remove amino groups. 11.3 Transport of Nitrogen to Liver and Kidney 11.3.1 Protein is degraded on a regular basis. 11.3.2 Amino acids are transported from muscle after proteolysis. 11.3.3 Ammonia is released in the liver and kidney. 11.4 Urea Cycle 11.4.1 The nitrogens of urea come from ammonia and aspartate. 11.4.2 The synthesis of urea requires five enzymes 11.4.2.1 Carbamoyl phosphate synthetase I 11.4.2.2 Ornithine transcarbamoylase 11.4.2.3 Argininosuccinate synthetase 11.4.3.4 Argininosuccinate lyase. 11.4.3.5 Arginase. 11.4.3 Urea synthesis is regulated by an allosteric effector (N-acetylglutamate) and enzyme induction. 11.4.4 Metabolic disorders of urea synthesis have serious results. 11.5 Synthesis and Degradation of Individual Amino Acids 11.5.1 Glutamate is a precursor of glutahione and -aminobutyrate. 11.5.2 Arginine is also synthesized in intestines. 11.5.3 Ornithine and proline are both synthesized from glutamate. 11.5.4 Serine and glycine are synthesized from 3-phosphoglycerate. 11.5.5 Tetrahydrofolate is a cofactor in many reactions of amino acids as a one-carbon carrier. 11.5.6 Threonine is usually metabolism to lactate. 11.5.7 Phenylalanine and tyrosine 11.5.7.1 Tyrosine is the first intermediate in phenylalanine metabolism. 11.5.7.2 Dopamine, epinephrine, and norepinephrine are derivatives of tyrosine. 11.5.7.3 Tyrosine is involved in synthesis of melanin, thyroid hormone, and quinoproteins. 11.5.8 Methionine and cysteine 11.4.8.1 Methionoine is an essential amino acid. 11.4.8.2 Cysteine is made from serine. 11.4.8.2.1 Methionine first reacts with ATP. 11.4.8.2.2 S-Adenosylmethioine is a methyl groups donor.
11.4.8.2.3 AdoMet is the precursor of spermidine and spermine. 11.4.8.2.4 Metabolism of cysteine produces sulfur-containg compounds. 11.5.9 Tryptophan (See Fig. 11.66) 11.5.9.1 Tryptophan is a precursor of NAD. 11.5.9.2 Pyridoxal phosphate has a prominent role in tryptophan metabolism. 11.5.9.3 Kynurenine gives rise to neurotransmitters. 11.5.9.4 Serotonin and melatonin are tryptophan derivatives. 11.5.9.5 Tryptophan induces sleep. 11.5.9.6 Initial reaction of BCAA (branched chain) metabolism are shared. 11.5.9.7 Pathways of valine and isoleucine metabolism are similar. 11.5.9.8 The leucine pathway differs from those of the other two branched-chain amino acids. 11.5.9.9 Propionyl CoA is metabolized to succinyl CoA. 11.5.10 Lysine 11.5.10.1 Carnitine is derived from lysine 11.5.11 Histidine 11.5.11.1 Urinary formiminoglutamate is diagnostic for folate deficieny. 11.5.11.2 Histiamine, carnosine, and anserine are produced from histidine. 11.5.11.3 Creatine 11.5.12 Glutahtionine 11.5.12.1 Glutathione is synthesized from three amino acids. 11.5.12.2 The -glutamyl cycle transports amino acids. 11.5.12.3 Glutathione concentration affects the response to toxins.
Clinical Correlations cc 11.1 Carbamoylphosphate Synthetase and N-Acetylglutamate Synthetase Deficiencies cc 11.2 Deficiencies of Urea Cycle Enzymes cc 11.3 Nonketotic Hyperglycinemia cc 11.4 Folic Acid Deficiency cc 11.5 Phenylketonuria cc 11.6 Disorders of Tyrosine Metabolism cc 11.7 Parkinson's Disease cc 11.8 Hyperhomocysteinemia and Atherogenesis cc 11.9 Other Diseases of Sulfur Amino Acids cc 11.10 Diseases of Metabolism of Branched Chain Amino Acids cc 11.11 Diseases of Propionate and Methylmalonate Metabolism cc 11.12 Diseases Involving Lysine and Ornithine cc 11.13 Histidinemia cc 11.14 Diseases of Folate Metabolism
12.1.1 The author of this chapter limited his discussion to only humans. 12.2 Metabolic Functions of Nucleotides 12.2.1 Roles of nucleotidetides 12.2.1.1 Energy metabolism 12.2.1.2 Monomeric units of nucleic acids 12.2.1.3 Regulators 12.2.1.4 Precursors 12.2.1.5 Components of coenzymes (This is a subclass of 4) 12.2.1.6 Activated intermediates (Similar to1) 12.2.1.7 Allosteric effectors (I consider this a subclass of 3) 12.2.2 The distribution of nucleotides vary with cell type. 12.3 Chemistry of Nucleotides 12,3,1 Properties of nucleotides 12.3.1.1 Absorb UV light 12.3.1.2 RNA digested by base. 12.4 Metabolism of Purine Nucleotides 12.4.1 The purine nucleotides are synthesized by a series of reactions to form IMP. See fig 12.7. 12.4.2 IMP is the common precursor for AMP and GMP. See Fig. 12.10/ 12.4.3 Purine nucleotide synthesis is highly regulated. 12.4.4 Purine bases and nucleotides can be salvaged to reform nucleotides. 12.4.5 Purine nucleotides can be interconverted to maintain the appropriate balance of adenine and guanine nucleotides. 12.4.6 GTP is a precursor of tetrahydrobiopterin. 12.4.7 The end product of purine degradation in humans is uric acid. 12.4.8 Uric acid is formed by xanthine oxidase action. 12.5 Metabolism of Pyrimidine Nucleotides 12.5.1 Pyrimidine nucleotides are synthesized by a series of reaction leading to UMP. See Fig 12.17. 12.5.2 Pyrimidine nucleotide synthesis in humans is regulated at the level of carbamoyl phosphate synthetase II. 12.5.3 Pyrimidine bases are salvaged to reform nucleotides. 12.6 Deoxyribonucleotide Formation 12.6.1 Deoxyribonucleotides are formed by reduction of ribonucleotide diphopsphates. 12.6.2 Deoxythymidylate synthesis requires N5,N10-methylene tetrahydrofolate. 12.6.3 Pyrimidine interconversions emphasize deoxyribopyrimidine nucleotiside and nucleotides. 12.6.4 Pyrimidne nucleotides are degraded to -amino acids. 12.7 Nucleoside and Nucleotide Kinases 12.7.1 ATP can donate a phosphate to form the other NTPs. 12.8 Nucleotide Metabolizing Enzymes as a Function of the Cell Cycle and Rate of Cell Division 12.8.1 Enzymes of purine and pyrimidine nucleotide synthesis are elevated during the S phase of the cell cycle.
12.9 Nucleotide Coenzyme Synthesis 12.9.1 FAD see Fig. 12.33. 12.9.2 CoA see Fig. 12.34. 12.10 Synthesis and Utilization of 5-Phosphoribosyl-1-pyrophosphate 12.10.1 De novo synthesis of purines. 12.10.1.1 Synthesis of 5-phosphoribosylamine. 12.10.2 Salvage of purine bases 12.10.3 De novo synthesis of pyrimidines. 12.10.4 Salvage of pyrimdines. 12.10.5 Synthesis of NAD+. 12.11 Compounds that Interfere with Cellular Purine and Pyrimidine Nucleotide Metabolism: Chemotherapeutic Agents 12.11.1 Antimetabolites are often structural analogs of bases or nucleosides. 12.11.2 Antifolates inhibit formation of tetrahydrofolate. 12.11.3 Glutamine anatgonists inhibit enzymes that utilize glutamine as nitrogen donors. 12.11.4 Other agents inhibit cell growth by interfering with nucleotide metabolism. 12.11.5 Purine and pyrimidine analogs can be antivirals. 12.11.6 Resistance against these agents can develop.
Clinical Correlations cc 12.1 Gout cc 12.2 Lesch-Nyhan Syndrome cc 12.3 Immunodeficiency Diseases Associated with Defects in Purine Nucleoside Degradation cc 12.4 Hereditary Orotic Aciduria
13.2.5.2 Liver provides glutathione for other tissues. 13.2.5.3 Kidney and liver provide carnitine for other tissues. 13.2.6 Energy requirements, reserves, and caloric homeostasis 13.2.7 Glucose homeostasis has five stages. See Fig. 13.10. 13.3 Mechanisms Involved in Switching the Metabolism of Liver Between the Well-Fed State and the Starved State 13.3.1 Substrate availability controls many metabolic pathways. 13.3.2 Negative and positive allosteric effectors regulate key enzymes. 13.2.3 Covalent modificaiton and demodification regulates key enzymes. 13.2.4 Changes in levels of key enzymes are a longer term adaptive mechanism. 13.4 Metabolic Interrelationships of Tissues in Various Nutritional and Hormonal States 13.4.1 Staying in the well-fed state results in obesity and insulin resistance. 13.4.2 Noninsulin-dependent diabetes mellitus 13.4.3 Insulin-dependent diabetes mellitus 13.4.4 Aerobic and anaerobic exercise use different fuels. 13.4.5 Changes in pregnancy are related to fetal requirements and hormonal changes. 13.4.6 Lactation requires synthesis of lactose, triacyglycerol, and protein 13.4.7 Stress and injury lead to metabolic changes. 13.4.8 Liver disease causes major metabolic derangements. 13.4.9 In renal disease nitrogenous wastes accumulate. 13.4.10 Oxidation of ethanol in liver alters the NAD+/NADH ratio. 13.4.11 In acid-base regulation, glutamine plays a pivotal role. 13.4.12 The colon salvages energy from the diet.
Clinical Correlations cc 13.1 Obesity cc 13.2 Protein Malnutrition cc 13.3 Starvation cc 13.4 Reye's Syndrome cc 13.5 Hyperglycemic, Hyperosmolar Coma cc 13.6 Hyperglycemia and Protein Glycosylation cc 13.7 Noninsulin-Dependent Diabetes Mellitus cc 13.8 Insulin-Dependent Diabetes Mellitus cc 13.9 Complications of Diabetes and the Polyol Pathway cc 13.10 Cancer Cachexia
14.2.3 Periodicity leads to secondary structure/ 14.2.3.1 Forces that determine polynucleotide confomation. 14.2.3.1.1 Stacked 14.2.3.1.2 Hydrophobic 14.2.3.1.3 Dipole-induced dipole interactions 14.2.3.2 DNA double helix 14.2.4 Many factors stabilize DNA structure. 14.2.4.1 Denaturation 14.2.4.2 Renaturation 14.2.4.3 Hybridization 14.2.4.4 DNA probes 14.2.4.5 Heteroduplexes 14.3 Types of DNA Structure 14.3.1 Size of DNA is highly variable. 14.3.1.1 Techniques for determining DNA size 14.3.2 DNA may b3 linear or circular 14.3.2.1 Double-stranded circles 14.3.2.2 Single-stranded DNA 14.3.3 Circular DNA is a superhelix. 14.3.3.1 Geometric description of superhelical DNA. 14.3.3.2 Topoisomerases 14.3.4 Alternative DNA conformations 14.3.4.1 DNA bending 14.3.4.2 Cruciform DNA 14.3.4.3 Triple-standed DNA 14.3.4.4 Four-stranded DNA. 14.3.4.5 Slipped DNA. 14.3.5 Nucleoproteins of eukaryotes contain histones and nonhistone proteins. 14.3.5.1 Nucleosomes and polynucelosomes. 14.3.5.2 Polynucleosome packing into higher structures. 14.3.6 Nucleoproteins of prokaryotes are similar to those of eukaryotes. 14.4 DNA Structure and Function 14.4.1 Restriction endonuclease and palindromes 14.4.2 Most prokaryotic DNA codes for specific proteins. 14.4.3 Only a small percentage of eukaryotic DNA codes for structural genes. 14.4.4 Repeated sequences 14.4.4.1 Single-copy DNA 14.4.4.2 Moderately reiterated DNA 14.4.4.3 Highlky reiterated DNA 14.4.4.4 Inverted repeat DNA 14.4.5 Mitochondrial DNA.
Clinical Correlations cc 14.1 DNA Vaccines cc 14.2 Diagnostic Use of Probes in Medicine cc 14.3 Topoisomerases in Treatment of Cancer
cc 14.4 Hereditary Persistence of Fetal Hemoglobin cc 14.5 Therapeutic Potential of Triplex DNA Formation cc 14.6 Expansion of DNA Triple Repeats and Human Disease cc 14.7 Mutations of Mitochondrial DNA: Aging and Degenerative Diseases
1.5.10 DNA replication, repair, and transcription are closely coordinated. 1.6 DNA Recombination 15.5.1 Homologous recombination. 15.5.1.1. Enzymes and proteins that catalyze homologous recombination 1.6.6 Site-specific recombination. 1.6.7 Transposition. 1.7 Sequencing of Nucleotides in DNA 15.6.1 Restriction maps give the sequence of segm,ents of DNA.
Clinical Correlations cc 15.1 Mutations and the Etiology of Cancer cc 15.2 Defects in Nucleotide Excision Repair and Hereditary Diseases cc 15.3 DNA Ligase Activity and Bloom Syndrome cc 15.4 DNA Repair and Chemotherapy cc 15.5 Mismatch DNA Repair and Cancer cc 15.6 Telomerase Activity in Cancer and Aging cc 15.7 Inhibitors of Reverse Transcriptase in Treatment of AIDS cc 15.8 Immunoglobulin Genes Are Assembled by Recombination cc 15.9 Transposons and Development of Antibiotic Resistance cc 15.10 DNA Amplification and Development of Drug Resistance cc 15.11Nucleotide Sequence of the Human Genome
16.4.4.3 Termination 16.4.5 Transcription in eukaryotes involves many additional molecular events. 16.4.5.1 The nature of active chromatin. 16.4.5.2 Enhancers 16.4.5.3 Transcription of ribosomal RNA genes. 16.4.5.4 Transcription by RNA polymerase II. 16.4.5.5 Promoters for mRNA synthesis 16.4.5.6 Transcription by RNA polymerase III 16.5 Posttranscriptional Processing 16.5.1 Transfer RNA precursors are modified by cleavage, additions, and base modification. 16.5.1.1 Cleavage 16.5.1.2 Additions 16.5.1.3 Modified nucleosides 16.5.2 Ribosomal RNA processing releases the various RNAs from a longer polymer. 16.5.3 Messenger RNA processing requires maintenance of the coding sequence. 16.5.3.1 Blocking of the 5 terminus and poly(A) synthesis 16.5.3.2 Removal of introns from mRNA precursors. 16.5.3.3 Mutations in splicing signals cause human disease. 16.5.3.4 Alternate pre-mRNA splicing can lead to multiple proteins being made from a single DNA coding sequence. 16.6 Nucleases and RNA Turnover
Clinical Correlations cc 16.1 Staphylococcal Resistance to Erythromycin cc 16.2 Antibiotics and Toxins that Target RNA Polymerase cc 16.3 Fragile X Syndrome: A Chromatin Disease? cc 16.4 Involvement of Transcriptional Factors in Carcinogenesis cc 16.5 Thalassemia Due to Defects in Messenger RNA Synthesis cc 16.6 Autoimmunity in Connective Tissue Disease
17.2.6 Codon-anticodon interactions permit reading of mRNA. 17.2.6.1 Breaking the genetic code. 17.2.6.2 Mutations 17.2.7 Aminoacylation of tRNA activates amino acids for protein synthesis. 17.2.7.1 Specificity and fidelity of aminoacylation reactions. 17.3 Protein Biosynthesis 17.3.1 Translation is directional and colinear with mRNA. 17.3.2 Initiation of protein synthesis is a comp9lex process. 17.3.3 Elongation is the stepwise formation of peptide bonds. 17.3.4 Termination of polypeptide synthesis requires a stop codon. 17.3.5 Translation has significant energy cost. 17.3.6 Protein synthesis in mitochondria differs slightly. 17.3.7 Some antibiotics and toxins inhibit protein biosynthesis. 17.4 Protein Maturation: Modification, Secretion, and Targeting 17.4.1 Proteins for export follow the secretory pathway. 17.4.2 Glycosylation of proteins occurs in the endoplasmic reticulum and Golgi apparatus. 17.5 Organelle Targeting and Biogenesis 17.5.1 Sorting of proteins targeted for lysosomes occurs in the secretory pathway. 17.5.2 Import of protein by mitochondria requires specific signals. 17.5.3 Targeting to other organelles requires specific signals. 17.6 Further Posttranslational Protein Modifications 17.6.1 Insulin biosynthesis involves partial proteolysis. 17.6.2 Proteolysis leads to zymogen activation. 17.6.2.1 Amino acids can be modified after incorporation into proteins. See Table 17.10. 17.6.3 Collagen biosynthesis requires many posttranslational modifications. 17.6.3.1 Procollagem formation occurs in the endoplasmic reticulum and Golgi appartus. 17.6.3.2 Collagen maturation occurs extracellularly. 17.7 Regulation of Translation 17.8 Protein Degradation and Turnover 17.8.1 Intracelluar digestion of some proteins occurs in lysosomes. 17.8.2 Ubiquitin is a marker for an ATP-dependent proteolysis.
Clinical Correlations cc 17.1 Missense Mutation: Hemoglobin cc 17.2 Disorders of Terminator Codons cc 17.3 Thalassemia cc 17.4 Mutation in Mitochondrial Ribosomal RNA Results in Antibiotic-Induced Deafness cc 17.5 I Cell Disease cc 17.6 Familial Hyperproinsulinemia cc 17.7 Absence of Posttranslational Modification: Multiple Sulfatase Deficiency cc 17.8 .Defects in Collagen Synthesis
cc 17.9 Deletion of a Codon, Incorrect Posttranslational Modification, and Premature Protein Degradation: Cystic Fibrosis
18.9.1 Bacteriophage as cloning vectors. 18.9.2 Screening bacteriophage libraries. 18.9.3 Cloning DNA fragments into cosmid and yeast artificial chromosome vectors. 18.10 Techniques to Further Analyze Long Stretches of DNA 18.10.1 Subcloning permits definition of large segments of DNA. 18.10.2 Chromosome walking is a technique to define gene arrangement in long stretches of DNA. 18.11 Expression Vectors and Fusion Proteins 18.11.1 Foreign genes can be expressed in bacteria allowing synthesis of their encoded proteins. 18.12 Expression Vectors in Eukaryotic Cells 18.12.1 DNA elements required for expression of vectors in mammalian cells. 18.12.2 Transfected eukaryotic cells can be selected by utilizing mutant cells that require specific nutrients. 18.12.3 Foreign genes can be expressed in eukaryotic cells by utilizing virus transformed cells. 18.13 Site Directed Mutagenesis 18.13.1 Role of flanking regions in DNA can be evaluated by deletion and insertion mutations. 18.13.2 Site-directed mutagenesis of a single nucleotide. 18.14 Applications of Recombinant DNA Technologies 18.14.1 Antisense nucleic acids hold promise as research tools and in therapy 18.14.2 Normal genes can be introduced into cells with a defective gene in gene therapy. 18.14.3 Transgenic animals 18.14.4 Recombinant DNA in agricultural will have significant commercial impact. 18.15 Concluding Remarks
Clinical Correlations cc 18.1Polymerase Chain Reaction and Screening for Human Immunodeficiency Virus cc 18.2 Restriction Mapping and Evolution cc 18.3 Direct Sequencing of DNA for Diagnosis of Genetic Disorders cc 18.4 Multiplex PCR Analysis of HGPRTase Gene Defects in Lesch-Nyhan Syndrome cc 18.5 Restriction Fragment Length Polymorphisms Determine the Clonal Origin of Tumors cc 18.6 Site-Directed Mutagenesis of HSV IgD cc 18.7 Normal Genes Can be Introduced into Cells with Defective Genes in Gene Therapy cc 18.8 Transgenic Animal Models
19.3.1 Repressor of the lactose operon is a diffusible protein. 19.3.2 Operator sequence of the lactose operon is contiguous on DNA with a promoter and three structural genes. See Fig. 19.4. 19.3.3 Promoter sequence of lactose operon contains recognition sites for RNA polymerase and a regulator protein. 19.3.4 Catabolite activator protein binds at a site on the lactose promotor. 19.4 Tryptophan Operon of E. coli 19.4.1 The tryptophan operon is controlled by a repressor protein. 19.4.2 The tryptophan operon has a second control site: the attenuator site. 19.4.3 Transcription attenuation is a mechanism of control in operons for amino acid biosynthesis. 19.5 Other Bacterial Operons 19.5.1 Synthesis of ribosomal proteins is regulated in a coordinated manner. 19.5.2 The stringent response controls synthesis of rRNAs and tRNAs. 19.6 Bacterial Transposons 19.6.1 Transposons are mobile segments of DNA. 19.6.2 The Tn3 transposon contains three structural genes. 19.7 Inversion of Genes in Salmonella 19.8 Organization of Genes in Mammalian DNA 19.8.1 Only a small fraction of eukaryotic DNA codes for proteins. 19.8.2 Eukaryotic genes usually contain interventing sequences (introns). 19.9 Repetitive DNA Sequences in Eukaryotes 19.9.1 The importance of highly repetitive sequences is unknown. 19.9.2 A variety of repeating units are defined as moderately repetitive sequences. 19.10 Genes for Globin Proteins 19.10.1 Recombinant DNA technology has been used to clone genes for many eukaryotic processes. 19.10.2 Sickle cell anemia is due to a single base pair change. 19.10.3 Thalassemias are caused by mutations in genes for the or subunits of globin. 19.11 Genes for Human Growth Hormone-like Proteins 19.12 Mitochondrial Genes. See Fig. 19.27. 19.13 Bacterial Expression of Foreign Genes 19.13.1 Recombinant bacteria can synthesize human insulin. 19.13.2 Recombinant bacteria can synthesis human growth hormone. 19.14 Introduction of Rat Growth Hormone Gene into Mice
Clinical Correlations cc 19.1 Transmissible Multiple Drug Resistances cc 19.2 Duchenne/Becker Muscular Dystrophy and the Dystrophin Gene cc 19.3 Prenatal Diagnosis of Sickle Cell Anemia cc 19.4 Prenatal Diagnosis of Thalassemia cc 19.5 Leber Hereditary Optic Neuropathy (LHON) cc 19.6 Huntington Disease and Unstable Trinucleotide Expansions
20.12 Intracellular Action: Protein Kinases 20.12.1 Insulin receptor: transduction through tyrosine kinase 20.12.2 Activity of vasopressin: protein kinase A. 20.12.3 Gonadotropin-releasing hormone (GnRH): Protein kinase C 20.12.4 Activity of atrial natriuretic factor (ANF): protein kinase G. 20.13 Oncogenes and Receptor Functions 20.13.1 The known oncogenes are summarized in Table 20.9.
Clinical Correlations cc 20.1 Testing Activity of the Anterior Pituitary cc 20.2 Hypopituitarism cc 20.3 Lithium Treatment of Manic Depressive Illness: The Phosphatidylinositol Cycle
22.5.11 The allosteric role of thrombin in controlling coagulation. 22.5.12 Inhibitors of the plasma serineproteinases. 22.5.13 Fibrinolysis requires plaminogen and tissue plasminogen activator to produce plasmin.
Clinical Correlations cc 22.1 Lambert Eaton Myasthenic Syndrome cc 22.2 Myasthenia Gravis: A Neuromuscular Disorder cc 22.3 Macula Degeneration Other Causes of Loss of Vision cc 22.4 Niemann Pick Disease and Retinitis Pigmentosa cc 22.5 Retinitis Pigmentosa Resulting from a de Novo Mutation in the Gene Codingfor Peripherin cc 22.6 Chromosomal Location of Genes for Vision cc 22.7 Troponin Subunits as Markers for Myocardial Infarction cc 22.8 Voltage Gated Ion Channelopathies cc 22.9 Intrinsic Pathway Defects Prekallikrein Deficiency cc 22.10 Classic Hemophilia cc 22.11 Thrombosis and Defects of the Protein C Pathw
cc 23.3 Deficiency of Cytochrome P450 21 Hydroxylase cc 23.4 Steroid Hormone Production During Pregnancy cc 23.5 Clinical Aspects of Nitric Oxide Production
26.5.1 Do- and polysaccharides require hydrolysis. 26.5.2 Monosaccharides are absorbed by carrier-mediated transport. 26.6 Digestion and Absorption of Lipids 26.6.1 Lipid digestion requires overcoming the limited water solubility of lipids. 26.6.2 Lipids are digested by gastric and pancreatic lipases. 26.6.3 Bile acid micelles solubilize lipids during digestion. 26.6.4 Most absorbed lipids are incorporated into chylomicrons 26.7 Bile Acid Metabolism
Clinical Correlations cc 26.1 Cystic Fibrosis cc 26.2 Bacterial Toxigenic Diarrheas and Electrolyte Replacement Therapy cc 26.3 Neutral Amino Aciduria (Hartnup Disease) cc 26.4 Disaccharidase Deficiency cc 26.5 Cholesterol Stones cc 26.6 A--Lipoproteinemia
27.8 Fiber 27.9 Composition of Macronutrients in the Diet 27.9.1 Composition of the diet affect serum cholesterol. 27.9.2 Effects of refined carbohydrate in the diet are not straightforward. 27.9.3 Mixed vegetable and animal proteins meet nutritional protein requirements. 27.9.4 An increase in fiber from varied sources is desirable. 27.9.5 Current recommendations are for a prudent diet. See Fig. 27.3.
Clinical Correlations cc 27.1 Vegetarian Diets and Protein-Energy Requirements cc 27.2 Low-Protein Diets and Renal Disease cc 27.3 Providing Adequate Protein and Calories for the Hospitalized Patient cc 27.4 Carbohydrate Loading and Athletic Endurance cc 27.5 High-Carbohydrate versus High-Fat Diets for Diabetics cc 27.6 Polyunsaturated Fatty Acids and Risk Factors for Heart Disease cc 27.7 Metabolic Adaptation: The Relationship between Carbohydrate Intake and Serum Triacylglycerols
28.7.1 Folic acid functions as tetrahydrofolate in one-carbon metabolism. 28.7.2 Vitamin B12 (cobalamine) contains cobalt in a tetrapyrrole ring. 28.8 Other Water-Soluble Vitamins 28.8.1 Ascorbic acid functions in reduction and hydroxylation reactions. 28.8.2 Lipoic acid function in -keto acid metabolism. 28.9 Macrominerals 28.9.1 Calcium has many physiological roles. 28.9.2 Magnesium is another important macromineral. 28.10 Trace Minerals 28.10.1 Iron is efficiently reutilized. 28.10.2 Iodine is incorporated into thyroid hormones. 28.10.3 Zinc is a cofactor for many enzymes. 28.10.4 Copper is also a cofactor for important enzymes. 28.10.5 Chromium is a component of glucose tolerance factor. 28.10.6 Selenium is a scavenger of peroxides. 28.10.7 Manganese, molybdenum, fluoride, and boron are other trace elements. 28.11 The American Diet: Fact and Fallacy 28.12 Assessment of Nutritional Status in Clinical Practice
Clinical Correlations cc 28.1 Nutritional Considerations for Cystic Fibrosis cc 28.2 Renal Osteodystrophy cc 28.3 Nutritional Considerations in the born cc 28.4 Anticonvulsant Drugs and Vitamin Requirements cc 28.5 Nutritional Considerations in the Alcoholic cc 28.6 Vitamin B6 Requirements for Users of Oral Contraceptives cc 28.7 Diet and Osteoporosis cc 28.8 Nutritional Considerations for Vegetarians cc 28.9 Nutritional Needs of Elderly Persons