Purine Metabolism in Man: Biochemistry and Pharmacology of Uric Acid Metabolism (Advances in Experimental Medicine and Biology)

Gout and urie acid lithiasis are known to have affected mankind for thousands of years. It is only recently, however, that great progress has been made in the understanding of the processes involved in purine metabolism and its disorders in man. The key enzymes active in the various pathways of purine synthesis and degradation have become known and their properties are the subject of intensive study. Major contributions to the knowledge of normal purine metabolism in man have derived from the study of inborn errors in patients with purine disorders, specifically complete and partial hypoxanthine-guanine phosphoribosyltransferase deficiency. Mutations of other enzymes involved in purine metabolism are being discovered. A great step forward has been made in the treatment of gout with the introduction of uricosuric drugs and more recently of the hypoxanthine analogue allopurinol, a synthetic xanthine oxidase inhibitor. Furthermore, the complex nature of the renal handling of urie acid excretion, although still posing difficult problems, appears to approach clari­ fication. Front Matter....Pages i-xvi Front Matter....Pages xxiii-xxiii The Kinetics of Intramolecular Distribution of 15 N in Uric Acid Following Administration of 15 N-Glycine: Preferential Labeling of N−(3+9) of Uric Acid in Primary Gout and a Reappraisal of the “Glutamine Hypothesis”....Pages 371-393 Hyperglutamatemia in Primary Gout....Pages 395-399 Reduced Renal Ammoniagenesis in Primary Gout....Pages 401-405 The Uptake of Glycine- 14 C into the Adenine and Guanine of DNA and Insoluble RNA of Human Leucocytes....Pages 407-416 In Certain Physiological Stress Conditions on the Problem of Hyperuricemia....Pages 419-421 Uric Acid Metabolism Following Acute Myocardial Infarction....Pages 423-427 The Effect of Weight Reduction on Urate Metabolism....Pages 429-433 Diet and Gout....Pages 435-442 Effect of Ribomononucleotides Given Orally on Uric Acid Production in Man....Pages 443-449 Relationship Between Gout and Arterial Hypertension....Pages 451-459 Studies on the Mechanism of Fructose-Induced Hyperuricemia in Man....Pages 463-470 Observations of Altered Intracellular Phosphoribosylpyrophosphate (PP-Ribose-P) in Human Disease....Pages 471-478 Human Erythrocyte Phosphoribosylpyrophosphate Content and “Generation” During a Constant Rate Infusion of Xylitol....Pages 479-482 Diabetes and Uric Acid — A Relationship Investigated by the Epidemiological Method....Pages 483-484 Metabolic and Glucose Load Studies in Uric Acid, Oxalic and Hyperparathyroid Stone Formers....Pages 485-494 Observations Concerning the Incidence of Disturbance of Lipid and Carbohydrate Metabolism in Gout....Pages 495-498 Gout and Hyperlipidaemia....Pages 499-508 Lipid and Purine Metabolism in Benign Symmetric Lipomatosis....Pages 509-516 An Integrative Hypothesis for the Renal Disease of Urate Overproduction....Pages 519-522 Acute Intratubular Crystal Deposition Causing Permanent Renal Damage in the Pig....Pages 523-534 Front Matter....Pages xxiii-xxiii Analysis of Treatment Results in Uric Acid Lithiasis with and without Hyperuricemia....Pages 535-540 Isolation of a Red Pigment from the Uric Acid Calculi....Pages 541-544 Concentration of Urate by Differential Diffusion: A Hypothesis for Initial Urate Deposition....Pages 547-550 Experimental Hyperuricemia in Rats....Pages 551-554 The Binding of Urate to Plasma Proteins....Pages 557-566 Front Matter....Pages 567-567 Efficacy of Single Daily Dose Allopurinol in Gouty Hyperuricemia....Pages 571-575 Withdrawal of Allopurinol in Patients with Gout....Pages 577-579 Effect of Long-Term Allopurinol Administration on Serial GFR in Normotensive and Hypertensive Hyperuricemic Subjects....Pages 581-596 Metabolic Studies of Thiopurinol in Man and the Pig....Pages 597-605 Effects of Allopurinol and Oxipurinol on Pyrimidine Biosynthesis in Man....Pages 609-619 The Molecular Basis for the Effects of Allopurinol on Pyrimidine Metabolism....Pages 621-628 Purine and Pyrimidine Biosynthesis in Neurospora Crassa and Human Skin Fibroblasts. Alteration by Ribosides and Ribotides of Allopurinol and Oxipurinol....Pages 629-635 Effects of Allopurinol and Oxonic Acid on Pyrimidine Metabolism in the Pig....Pages 637-638 Ribonucleotides of Allopurinol and Oxipurinol in Rat Tissues and Their Significance in Purine Metabolism....Pages 639-652 The Effect of Allopurinol on Oral Purine Absorption and Excretion in the Pig....Pages 653-655 Allopurinol and Thiopurinol : Effect in vivo on Urinary Oxypurine Excretion and Rate of Synthesis of their Ribonucleotides in Different Enzymatic Deficiencies....Pages 657-662 Urinary Excretion of 6 Hydroxylated Metabolite and Oxypurines in a Xanthinuric Man Given Allopurinol or Thiopurinol....Pages 663-667 Acute Renal Failure During Adenine Therapy in Lesch-Nyhan Syndrome....Pages 671-675 Behavioural Changes During Adenine Therapy in Lesch-Nyhan Syndrome....Pages 677-679 Treatment of Gout and Hyperuricaemia by Benzbromarone Ethyl 2 (Dibromo -3,5 Hydroxy - 4 Benzoyl) - 3 Benzofuran....Pages 683-689 Front Matter....Pages 567-567 The Pig as an Animal Model for Purine Metabolic Studies....Pages 691-692 Influence of a Uricosuric Drug on Connective Tissue Metabolism....Pages 693-698 The Synthesis and Immuno-Enhancing Activity of 3-Butylazathioprine....Pages 699-704 Front Matter....Pages 705-705 The Clinical Significance of Hypouricemia....Pages 709-716 Hypouricemia, Hypercalciuria, and Decreased Bone Density. A New Hereditary Syndrome....Pages 717-721 Suppression of Uric Acid Secretion in a Patient with Renal Hypouricemia....Pages 723-728 Evidence for a Urate Reabsorptive Defect in Patients with Wilson’s Disease....Pages 729-737 Reevaluation of the Pyrazinamide Suppression Test....Pages 739-744 Evidence for a Post-Secretory Reabsorptive Site for Uric Acid in Man....Pages 745-749 Uric Acid Excretion in Infancy....Pages 753-757 Renal Handling of Uric Acid in Sickle Cell Anemia....Pages 759-762 Hyperuricemia Induced by Ethambutol....Pages 763-767 Uricosuric Effect of an Anticholinergic Agent in Hyperuricemic Subjects....Pages 769-776 Effects of Benzofuran Derivatives on Tubular Permeability to Urate-2- 14 C in the Rat Nephron....Pages 777-780 The Effect of Glucose upon Reabsorptive Transport of Urate by the Kidney....Pages 781-787 Mechanisms of Renal Excretion of Urate in the Rat....Pages 789-790 Front Matter....Pages 791-791 Immunoadsorbent Chromatography of Hypoxanthine-Guanine Phosphoribosyltransferase....Pages 793-797 The Use of High Pressure Liquid Chromatography to Monitor Nucleotide Levels in Cells....Pages 799-806 Electrophoretic Separation of Normal and Mutant Phosphoribosylpyrophosphate Synthetase....Pages 807-809 Development of a Micro HG-PRT Activity Assay: Preliminary Complementation Studies with Lesch — Nyhan Cell Strains....Pages 811-815 Front Matter....Pages 791-791 Comment on the Assay of Purine Phosphoribosyltransferases in Cultured Human Fibroblasts....Pages 817-820 Significance of Staining Uric Acid Crystals with Natural and Synthetic Dyes....Pages 821-833 Back Matter....Pages 835-846 Gout and uric acid lithiasis are known to have affected mankind for thousands of years. It is only recently, however, that great progress has been made in the understanding of the processes involved in purine metabolism and its disorders in man. The key enzymes active in the various pathways of purine synthesis and degradation have become known and their properties are the subject of intensive study. Major contributions to the knowledge of normal purine metabolism in man have derived from the study of inborn errors in patients with purine disorders, specifically complete and partial hypoxanthine-guanine phosphoribosyltransferase deficiency. Mutations of other enzymes involved in purine metabolism are being discovered. A great step forward has been made in the treatment of gout with the introduction of uricosuric drugs and more recently of the hypoxanthine analogue allopurinol, a synthetic xanthine oxidase inhibitor. Furthermore, the complex nature of the renal handling of uric acid excretion, although still posing difficult problems, appears to approach clari fication