Uric acid

著者

• Arnold, William James
• Kelley, William N.
• Weiner, Irwin M.

書誌事項

Uric acid

contributors, W.J. Arnold ... [et al.] ; editors, William N. Kelley, Irwin M. Weiner

（Handbook of experimental pharmacology, v. 51）

Springer-Verlag, 1978

• : us
• : gw

注記

Includes bibliographies and indexes

内容説明・目次

内容説明

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.

目次

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.- 1. Microinjection Technique.- 2. Microperfusion of Tubular Segments In Vivo.- 3. Microperfusion of Isolated Tubular Segments from Rabbits In Vitro.- 4. Free-flow Micropuncture.- 5. Uptake of Uric Acid by Renal Tissue.- V. Analytic Methods Used for Measuring Urate Concentrations in Body Fluids.- VI. Overall Renal Function and Plasma Concentrations of Uric Acid in Various Mammalian Species.- C. Rabbit.- I. Ultrafilterability of Urate.- II. Fractional Excretion of Urate.- III. Micropuncture Studies and Microperfusion of Isolated Tubular Segments.- IV. Uptake of Urate into Renal Cortical Tissue In Vitro.- V. Drug Effects.- VI. Conclusion.- D. Dog.- I. Comparison of Dalmatian and Non-Dalmatian Dogs.- II. Effects of Drugs.- III. Conclusion.- E. Rat.- I. Plasma Concentration and Ultrafilterability of Urate.- II. Fractional Excretion of Urate.- III. Site and Nature of Transtubular Movements of Urate.- 1. Proximal Convoluted Tubules.- 2. Henle's Loops.- 3. Distal Convoluted Tubules.- 4. Collecting Ducts.- IV. Effects of Drugs.- V. Experimental Hyperuricemia.- VI. Conclusion.- F. Mouse.- G. Guinea Pig.- H. Pig.- J. Nonhuman Primates.- I. Old-World Monkeys.- II. New-World Monkeys.- 1. Effects of Drugs and Metabolites.- III. Apes.- IV. Conclusion.- K. Isolated Data on Other Species of Mammals.- L. Conclusions.- References.- 10 Urate Excretion in Man, Normal and Gouty.- A. Introduction.- B. Development of Concepts of Renal Urate Handling.- C. Factors Thought to Affect Urate Excretion in Normal Man.- I. Sequence of Renal Reabsorptive and Secretory Transport Sites.- II Plasma Urate and GFR.- III. Urate Binding by Plasma Proteins.- IV. Extracellular Fluid Volume and the Renal Circulation.- V. Urine Flow.- VI. Urine pH.- VII. Angiotensin and Other Vasoactive Substances.- VIII. Relation of Urate Transport to Other Organic Compounds.- IX. Possibility of Intrarehal Urate Synthesis.- X. Red Cell Uptake and Renomedullary Accumulation.- D. Urate Excretion in Gout.- I. Classification of Gout.- II. Chronic Renal Disease with Gout.- E. Conclusion.- References.- 11 Abnormal Urate Excretion Associated with Renal and Systematic Disorders, Drugs, and Toxins.- A. Introduction.- B. Renal Response to Increased Urate Production.- I. Over-Excretion with Over-Production of Urate.- II. Over-Excretion of Uric Acid Due to Dietary Variables, Especially Purine Consumption.- III. Over-Production with Under-Excretion of Urate.- C. Renal Causes of Abnormal Urate Metabolism.- I. Abnormal Renal Excretion of Urate not Associated with Chronic Disease.- 1. Genetic Tubular Dysfunction.- a) Urate-Losing Disorders.- b) Urate-Retaining Disorders.- 2. Reversible Tubular Dysfunction.- a) Metabolites.- b) Drugs.- c) Toxins.- II. Abnormal Renal Excretion of Urate Associated with Chronic Renal Disease.- D. Drugs Affecting Urate Excretion.- I. Drugs that have a Biphasic Action on Renal Excretion of Urate.- 1. Uricosuric Drugs.- 2. Aspirin.- 3. Diuretics.- 4. Pyrazinamide.- II. Drugs that Increase Renal Excretion of Urate.- III. Drugs that Reduce the Renal Excretion of Urate.- IV. Drugs that Alter Urate Excretion by Altering Urate Production.- 1. Drugs that Increase Urate Production.- 2. Drugs that Reduce Purine Production.- E. Systemic Conditions Leading to Abnormal Urate Metabolism.- I. Hypertension.- II. Obesity.- III. Regular Alcohol Consumption.- IV. Hyperlipidemia.- V. Degenerative Vascular Disease.- VI. Acute Myocardial Infarction.- VII. Diabetes.- VIII. Myxedema.- IX. Parathyroid Disease.- X. Glycogen Storage Disease.- XI. Fructose Administration.- XII. Toxemia of Pregnancy.- XIII. Liver Disease.- XIV. Sarcoidosis and Chronic Beryllium Disease.- XV. Respiratory Acidosis.- XVI. Psoriasis.- XVII. Infectious Mononucleosis.- XVIII. Estrogen Therapy.- XIX. Down's Syndrome.- XX. Hodgkin's Disease and Other Malignancies.- References.- Biochemistry and Physiology of Uric Acid: Extrarenal Disposal.- 12 Extrarenal Disposal of Uric Acid.- A. Introduction.- B. The Uricolytic Enzyme System.- C. Recovery of Injected Isotopic Uric Acid.- I. Recovery of Isotopic Uric Acid in Urine.- II. Recovery of Isotopic Uric Acid in Degradation Products.- D. Site of Uricolysis.- E. Extrarenal Excretion of Uric Acid.- F. Conclusion.- References.- Pathology of Uric Acid: Acute Gouty Arthritis.- 13 Initial Events in the Development of an Acute Attack of Gouty Arthritis.- A. Introduction.- B. How Do Crystals Appear in the Joint?.- I. Precipitation in Synovial Fluid.- II. Deposition in Synovial Membrane.- C. How Do Urate Crystals Induce Inflammation in the Joint?.- I. Why Do Crystals not Always Seem to Produce Inflammation?.- II. How Can Crystals Induce Inflammation After Arrival in the Joint Fluid ?.- 1. Intra-Articular Injection of Urates.- 2. In Vitro Studies of Crystal-Cell Interaction.- 3. Immunologic Contributions.- D. Conclusion.- References.- 14 Role of Proteoglycans in the Development of Gouty Arthritis.- A. Introduction.- B. Historical Background.- C. The Deposition Phenomenon: Modern Connective Tissue Concepts.- I. Solubility of Monosodium Urate in Bovine Tissues.- II. Detection of a Urate-Solubilizing Substance in Connective Tissue.- III. Solubility of Monosodium Urate in Polysaccharide Solutions.- IV. Inhibition of Urate Crystallization by Polysaccharides.- V. Induction of Urate Crystallization from Polysaccharide Solutions Saturated with Urate.- VI. Induction of Urate Crystallization from Human Synovial Fluid.- D. Speculations on Altered Connective Tissue Metabolism in Gout.- I. Normal Connective Tissue Metabolism.- II. Accelerated Connective Tissue Metabolism as a Cause of Urate Deposition.- E. Effect of Colchicine on Connective Tissue Metabolism.- F. Diagnostic Value of Serum Glycosaminoglycans Determination.- G. Conclusion.- References.- 15 Role of the Leukocyte and Chemical Mediators of the Acute Gouty Attack.- A. Phagocytosis of Crystals.- B. Mediators of the Inflammatory Response.- C. Termination of the Acute Gouty Attack.- References.- 16 Role of Local Factors in the Precipitation of Urate Crystals.- A. Introduction.- B. Temperature.- C. pH.- D. Cavitation.- E. Osteoarthritis.- F. Concentration.- G. Shoes.- H. Crystal Deposits.- J. Conclusion.- References.- Pathology of Uric Acid: Nephrolithiasis and Urate Nephropathy.- 17 Uric Acid Nephrolithiasis.- A. Introduction.- B. Prevalence of Uric Acid Nephrolithiasis.- C. Chemistry of Uric Acid.- D. Structure and Formation of Uric Acid Stones.- E. Association of Other Crystalline Constituents in Uric Acid Stones.- F. Pathogenesis of Uric Acid Nephrolithiasis.- I. Hyperuricosuria and Hyperuricemia.- II. Undue Urinary Acidity and Subnormal Ammonium Excretion.- III. Organic Matrix and Crystallization.- G. Natural History of Uric Acid Nephrolithiasis.- I. Primary Gout and Hyperuricemia Without Gout.- II. Uric Acid Lithiasis in Secondary Gout, Associated with Blood Dyscrasia.- III. Hypoxanthine Guanine Phosphoribosyl Transferase (HPRT) Deficiency and Other Enzyme Abnormalities.- IV. Chronic Renal Disease.- V. Chronic Ulcerative Colitis and Regional Ileitis.- VI. Idiopathic Uric Acid Lithiasis.- H. Detection of the Chemical Nature of the Stone.- J. Management of Uric Acid Nephrolithiasis.- I. Correction of Undue Urine Acidity.- 1. Adequate Hydration.- 2. Sensible Diet.- 3. Alkalinizing Agents.- II. Control of Infection.- III. Control of Hyperuricosuria-Allopurinol.- K. Conclusion.- References.- 18 Association of Calcium Nephrolithiasis with Disorders of Uric Acid Metabolism.- A. Introduction.- B. Frequency of Hyperuricosuria in Calcium Stone Formers.- C. Mechanisms of Hyperuricosuria.- I. Role of Diet.- II. Role of Over-Production.- III. Possible Renal Tubular Disturbance.- D. Natural History of Stone Disease.- E. Urate-Oxalate Epitaxis.- I. Crystallographic Evidence.- II. Heterogeneous Nucleation.- F. Reduced Urine Inhibitors.- G. Allopurinol Treatment.- H. Conclusion.- References.- 19 Pathology of Urate Nephropathy.- A. Introduction.- B. Gross Examination.- C. Acute Obstructive Uric Acid Nephropathy in Blood Dyscrasias and Neoplasms.- D. Experimental Production of Acute Uric Acid Nephropathy.- E. Structural Alterations in the Gouty Kidney.- F. Miscellaneous Observations.- G. Selected Laboratory Procedures.- I. Roentgenography.- II. Renal Biopsy.- H. Conclusion.- References.- Pharmacology of Uric Acid.- 20 Uricosuric Drugs.- A. Introduction.- B. Tubular Transport of Uricosuric Drugs.- C. Drug Metabolism.- D. Mechanisms of Uricosuria.- E. Clinical Pharmacology and Use.- F. Clinically Important Uricosuric Drugs.- I. Probenecid.- 1. Chemistry, Methods of Assay, and Pharmacokinetics.- 2. Biologic Effects.- 3. Toxicology.- II. Sulfinpyrazone and Related Pyrazolidinediones.- 1. Method of Assay.- 2. Pharmacokinetics.- 3. Biologic Effects.- 4. Toxicology.- III. Benzbromarone and Related Drugs.- 1. Pharmacokinetics and Assay.- 2. Biologic Effects.- 3. Toxicology.- IV. Tienilic Acid (Ticrynafen) and Other Uricosuric Diuretics.- 1. Pharmacokinetics and Assays.- 2. Biologic Effects.- 3. Toxicology.- References.- 21 Allopurinol and Other Inhibitors of Urate Synthesis.- A. Introduction.- B. Inhibition of Xanthine Oxidase In Vitro.- C. Inhibition of Xanthine Oxidase In Vivo.- I. Exogenous Purines.- II. Inhibition of Uric Acid Production.- III. Oxypurines.- D. Pharmacokinetics and Clearance.- E. Metabolism.- I. Plasma and Urinary Metabolites.- II. Tissue Metabolites-Nucleotides.- F. Effects on Purine Biosynthesis.- G. Effects on Pyrimidine Biosynthesis.- H. Other Pharmacological Effects.- I. Iron Metabolism.- II. Protection from Ischemia.- III. Tryptophan Pyrrolase Inhibition.- IV. Drug Interactions.- V. Reduction of Urinary Calculi.- J. Toxicology.- K. Other Xanthine Oxidase Inhibitors.- I. Thiopurinol.- II. Other.- References.- 22 Enzymatic Uricolysis and Its Use in Therapy.- A. Introduction.- B. Properties of Urate Oxidase.- C. Pharmacologic Action of Urate Oxidase.- D. Therapeutic Trials of Enzymatic Uricolysis.- I. Urate Oxidase in Primary Hyperuricemia.- 1. Primary Asymptomatic Hyperuricemia.- 2. Hyperuricemia with Gout.- 3. Lesch-Nyhan Syndrome.- II. Secondary Hyperuricemia.- 1. In Renal Impairment.- 2. In Hemopathies.- 3. In Obesity.- III. Ophthalmology.- E. Tolerance.- I. Clinical Tolerance.- II. Immunologic Reactions.- F. The Use of Uricolytic Therapy: Limits, Indicators, Methods.- References.- 23 Pharmacology of Drugs Used in Treatment of Acute Gout.- A. Introduction.- B. Colchicine.- I. Brief History.- II. Structure and Structure/Function Relationships.- III. Metabolism.- IV. Mechanism of Action.- V. Clinical Use.- VI. Toxicology.- C. Phenylbutazone and Oxyphenbutazone.- I. Structure and Function.- II. Metabolism.- III. Clinical Use.- D. Indomethacin.- I. Structure.- II. Metabolism.- III. Mechanism of Action.- IV. Clinical Use and Toxicity.- E. Naproxen.- I. Chemical Structure.- II. Metabolism.- III. Mechanism of Action.- IV. Clinical Use.- F. Fenoprofen.- I. Chemical Structure.- II. Metabolism.- III. Mechanism of Action.- IV. Clinical Use.- References.- Author Index.

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詳細情報

• NII書誌ID(NCID): BA06984733
• ISBN:
  • 0387086110
  • 3540086110
• LCCN: 77028641
• 出版国コード: gw
• タイトル言語コード: eng
• 本文言語コード: eng
• 出版地: Berlin ; New York
• ページ数/冊数: xxii, 639 p.
• 大きさ: 25 cm
• 分類:
  • LCC : QP905
  • LCC : RC629
  • DC : 615/.1/08 s
  • DC : 616/.6
• 件名:
  • LCSH : Gout
  • LCSH : Uric acid metabolism
• 親書誌ID:
  • BA00516120