Uric acid has attracted the attention of scientists from a broad spectrum of disciplines, and in recent years dramatic progress has occurred within many of these disciplines. This volume is designed to fill void in the field. Major works in the past five years have provided comprehensive reviews of disorders of uric acid metabolism for the clinical (1-3) as well as short reports of recent progress for the interested scholar (4, 5). In Uric Acid the reader will find extensive reviews of relevant topics selected largely by virtue of recent progress in the field and written by those who, to a considerable extent, qre responsible for that progress. Seven chapters are dedicated to a description of uric acid synthesis, its control, diseases resulting from aberrations in the pathway, and effects of intermediates and end products of this pathway on other metabolic processes. The next five chapters describe our current understanding of the mechanisms by which uric acid is elimi­ nated by the organism. Then seven chapters review the factors responsible for the human "disease" produced by uric acid in the joints and kidneys. The final four chapters provide a summary of therapeutic approaches to control gout, the most important disease caused per se by uric acid.

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Biochemistry and Physiology of Uric Acid: Production.- 1 Uric Acid: Chemistry and Synthesis.- A. Introduction.- B. Structure.- C. Properties.- D. Synthesis.- I. Synthesis from Imidazoles.- II. One-Pot Synthesis.- E. Biosynthesis of Purines.- F. Uricotelism.- G. Uricolysis.- H. Measurement of Uric Acid Synthesis in Man.- J. Uric Acid Formation from Purines.- References.- 2 Regulation of Biosynthesis De Novo.- A. Introduction.- B. Rate-Limiting Step.- C. Enzymatic Activities Leading to PRA Synthesis.- D. Properties of Human PP-ribose-P Amidotransferase.- E. Studies with Intact Cells.- F. Studies In Vivo.- G. Conclusion.- References.- 3 Purine Salvage Enzymes.- A. Introduction.- B. Normal Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT).- I. Assay Methods and Kinetic Properties.- II. Physical Properties.- III. Role in Cellular Transport of Purines.- C. Clinical Syndromes Associated with a Deficiency of HGPRT.- I. Lesch-Nyhan Syndrome.- 1. Characteristics of the Mutant HGPRT in Patients with the Lesch-Nyhan Syndrome.- 2. Inheritance of HGPRT.- 3. Pathogenesis of the Neurobehavioral Disorder.- 4. Secondary Metabolic and Enzymatic Abnormalities.- II. Partial Deficiency of HGPRT.- 1. Characteristics of the Mutant HGPRT Enzyme in Patients with a Partial Deficiency of HGPRT Activity.- 2. Inheritance of Partial HGPRT Deficiency.- 3. Secondary Metabolic and Enzymatic Abnormalities.- D. Normal Adenine Phosphoribosyltransferase (APRT).- I. Assay Methods and Kinetic Properties.- II. Physical Properties.- III. Role in Cellular Transport of Purines.- E. Clinical Syndromes Associated with a Deficiency of APRT.- I. Partial Deficiency of APRT.- 1. Characteristics of the APRT Enzyme in Patients with a Partial Deficiency.- 2. Metabolic Abnormalities Associated with a Partial APRT Deficiency.- II. Complete Deficiency of APRT Activity.- References.- 4 Purine Nucleotide Interconversions.- A. Pathways of Purine Nucleotide Interconversion.- B. Regulation of Enzymes of Purine Nucleotide Interconversion in Intact Mammalian Cells.- I. Enzyme Amount and Localization.- II. Substrate Concentrations.- III. Alternative Pathways of Substrate Metabolism.- IV. Effects of Other Metabolites.- C. Functions of the Reactions of Purine Nucleotide Interconversion in Mammalian Cells.- I. Biosynthesis of ATP and GTP.- II. Balance Between ATP and GTP Concentrations.- III. Catabolism of Adenine and Guanine Nucleotides.- IV. Deamination of Amino Acids.- D. Effects of Drugs on the Reactions of Purine Nucleotide Interconversion.- References.- 5 Degradation of Purine Nucleotides.- A. Introduction.- B. Reactions of Purine Nucleotide Degradation.- C. Properties of Purine Catabolic Enzymes.- I. 5?-Nucleotidase(E.C.3.1.3.5) and Other Phosphatases.- II. Purine Nucleoside Phosphorylase (E.C.2.4.4.1.- III. Adenosine Deaminase (E.C.3.5.4.6).- IV. Guanine Deaminase (E.C.3.5.4.3).- V. Xanthine Oxidase (E.C.1.2.3.2).- D. Regulation of Purine Nucleotide Degradation.- E. Inborn Errors of Purine Nucleotide Degradation.- I. Adenosine Deaminase Deficiency.- II. Purine Nucleoside Phosphorylase Deficiency.- III. Xanthinuria.- IV. Other Disorders.- F. Relationship of Purine Nucleotide Degradation to Immune Function.- G. Other Relationships to Purine Nucleotide Degradation.- H. Conclusions.- References.- 6 Interrelationship of Purine and Pyrimidine Metabolism.- A. Introduction.- B. Control of Enzyme Activity by Pyrimidines in Purine Biosynthetic Pathways.- I. Phosphoribosyl Pyrophosphate Amidotransferase.- II. Adenylosuccinate Synthetase.- III. IMP Dehydrogenase.- IV. Adenosine Kinase.- C. Control of Enzyme Activity by Purines in Pyrimidine Biosynthetic Pathways.- I. Carbamoyl-Phosphate Synthetase II.- II. Aspartate Carbamoyltransferase.- III. Orotate Phosphoribosyltransferase.- IV. Orotidylate Decarboxylase.- V. Cytidine Triphosphate Synthetase.- VI. Uridine-Cytidine Kinase.- D. Regulation of the Ribonucleotide System.- E. Disorders in Nucleotide Biosynthesis Induced by Exogenous Purines and Pyrimidines.- I. Disorders in Purine Biosynthesis Induced by Orotate.- II. Inhibition of Pyrimidine Nucleotide Synthesis by Adenine.- III. Interference of Adenosine and Other Purine Nucleosides with Pyrimidine Biosynthesis.- IV. Effects of Allopurinol on Pyrimidine Biosynthesis De Novo.- F. Role of Cellular Levels of Phosphoribosyl Pyrophosphate in Coordinate Control of Purine and Pyrimidine Nucleotide Biosynthesis.- G. Possible Interrelationship Between Catabolism of Purine and Pyrimidine Nucleotides.- I. Dephosphorylation of Purine and Pyrimidine Mononucleotides.- II. Cleavage of Glycosidic Bond.- H. Possible Interference Between Purine and Pyrimidine Transport.- I. Conclusion.- References.- 7 Abnormalities of PRPP Metabolism Leading to an Overproduction of Uric Acid.- A. Introduction.- B. Metabolism of PRPP.- I. Utilization of PRPP.- II. Intracellular PRPP Concentration.- III. Determinants of PRPP Synthesis.- 1. PRPP Synthetase.- 2. Substrates.- 3. Inhibitors.- 4. Activators.- 5. Structure and Activity of PRPP Synthetase.- 6. Control of the Amount of PRPP Synthetase.- C. PRPP Availability and the Rate of Purine Synthesis De Novo.- I. Studies of Amidophosphoribosyltransferase and Its Effectors.- II. Effects of Pharmacologic Agents on PRPP Concentration and Purine Synthetic Rate.- D. Studies of PRPP Metabolism in Uric Acid Overproducers Without Recognized Enzyme Defects.- E. PRPP Metabolism in Enzyme Defects Associated with Uric Acid Overproduction.- I. Increased PRPP Production.- 1. Excessive PRPP Synthetase Activity.- 2. Glucose-6-phosphatase Deficiency.- 3. Increased Glutathione Reductase Activity.- II. Decreased PRPP Use.- 1. HGPRT Deficiency.- 2. APRT Deficiency.- 3. Purine Nucleoside Phosphorylase Deficiency.- References.- Biochemistry and Physiology of Uric Acid: Renal Disposal.- 8 Urate Excretion in Nonmammalian Vertebrates.- A. Introduction.- B. Occurrence of Urates as the Primary Excretory Products of Nitrogen Metabolism.- C. The Process of Renal Excretion of Urates.- I. Filtration at the Glomerulus.- II. Transport by the Renal Tubules.- 1. Direction of Net Urate Transport.- 2. Sites of Tubular Transport.- 3. Process of Tubular Transport.- 4. Specificity of Tubular Transport.- D. Chemical Forms of Urates in Urine.- I. Forms in Liquid Phase of Urine.- II. Forms in Urine Precipitates.- III. Modification of Form and Ionic Content of Urates by Transport Processes in Bladder or Cloaca.- E. Concluding Remarks.- References.- 9 Urinary Excretion of Uric Acid in Nonhuman Mammalian Species.- A. Introduction.- B. Methods of Investigation.- I. Clearance Methods.- II. Stop-flow Analysis.- III. The Double-Isotope-Precession Method.- IV. Micropuncture Methods…