Purine and Pyrimidine Metabolism in Man V : Part B: Basic Science Aspects

The Fifth International Symposium on Human Purine and Pyrimidine Metabolism was held in San Diego, California (U. S. A. ) in July and August of 1985. Previous meetings in this series were held in Tel Aviv (Israel), Baden (Austria), Madrid (Spain) and Maastricht (The Netherlands). The proceedings of each of these meetings were published by Plenum. The next meeting will be in Japan. This Symposium differed from those that went before in that it per­ mitted us to honor Dr. J. E. Seegmiller, Professor of Medicine at the University of California San Diego, for his many contributions to our understanding of purine metabolism in man. This publication is dedicated as a Festschrift to Jay. Dr. Richard W. E. Watts delivered the keynote address outlining in scholarly fashion the history of Dr. Seegmiller's accomplishments in research on purine metabolism and the great number of currently active scientists in this field who have worked with him. This address is published as the first contribution to Volume I. Dr. Dewitt Stetten, Jr. , was scheduled to be the speaker at our banquet. Unfortunate­ ly, he could not be with us. Dr. Seegmiller has written an appreciation of Dr. Stetten and his contributions to our field, and this has been pub­ lished following Dr. Watts' paper. The growth of knowledge in purine and pyrimidine metabolism continues to be exponential. The variety of subjects included in these volumes is impressive.

I. Adenosine Receptors.- Adenosine Receptors on Human T Lymphocytes and Human Thymocytes.- Adenosine Receptors on Human Lymphocytes.- Inhibition of Mast Cell Mediator Release by 5-Amino-4- Imidazolecarboxamide Riboside.- Purine Metabolism by Guinea Pig Ileum.- Suppression by Methylthioadenosine of Histamine or Leukotrienne-Induced Contraction in Isolated Guinea Pig Tracheal Rings.- Adenosine Receptors on Human Basophils and Lung Mast Cells.- II. Purine Receptors and the CNS.- Hypoxanthine Uptake by Isolated Brain Microvessels.- Morphine: Sites of Action in Guanosine Nucleoside Pathway.- Purine and Monoamine Metabolites in Cerebrospinal Fluid.- Characteristics of High Affinity and Low Affinity Adenosine Binding Sites in Human Cerebral Cortex.- III. Nucleoside and base Transport.- Hypoxanthine Transport Through Human Erythrocyte Membranes.- Regulatory Aspects of Hypoxanthine Uptake by Human Erythrocytes.- Mutant Mouse Cells with Nitrobenzulthioinosine-insensitive Nucleoside Transport Functions.- Carrier Mediated Uptake of Deoxyguanosine in Rat Liver Mitochondria.- IV. Studies with Anti-Metabolites.- Mechanism of Thymineless Death.- Enhancement of Methotrexate Cytotoxicity by Uracil Analogues that Inhibit Deoxyuridine Triphosphate Nucleotidohydrolase (dUTPase) Activity.- Influence of Methotrexate on Purine and Pyrimidine Pools and on Cell Phase Distribution of Cultured Human Lymphoblasts.- Modulation of Cytotoxicity and Metabolism of 5-Fluorouracil in Two Intestine Cell Lines.- Toxicity and Antitumor Effect of 5-Fluorouracil and Its Rescue by Uridine.- Synergy of Methotrexate and 6-Mercaptopurine in Cell Growth and Clonogenicity of Cultured Human T-Lymphoblasts.- Increased Availability of Phosphoribosyl Pyrophosphate as the Basis for Enhanced 6-Mercaptopurine Incorporation by Methotrexate, in Cultured Human Lymphoblasts.- Regulation of Deoxyadenosine and Nucleoside Analog Phosphorylation by Human Placental Adenosine Kinase.- The Biosynthesis of Deoxyguanosine Triphosphate in Herpes Simplex Type-1 Infected Vero Cells Treated with Acyclovir and Hydroxyurea.- 5-AZA-2’-Deoxycytidine Synergic Action with Thymidine on Leukemic Cells and Interaction of 5-AZA-dCMP with dCMP Deaminase.- Selection of Purine Nucleoside Analogs Based on Multiple Biological and Biochemical Parameters.- Effect of mAMSA on the Cellular Pharmacology of Ara-CTP in Human Leukemic Cells During Therapy with High- Dose Ara-C.- 5-Fluoro-5’-Deoxyuridine Is an Inhibitor of Uridylate Nucleotidase in L1210 Leukaemia.- V. Deoxynucleotide and Nucleoside Toxicity and Metabolism.- The Effect of Phosphonoformic Acid on Wild Type and Mutant S49 Cell Lines.- Mechanisms of Deoxyguanosine Toxicity for Human T and B Lymphocytes.- Role of Intracellular Deoxynucleoside Triphosphate Levels in DNA Repair in Human Lymphocytes.- Genetic Analysis of Deoxyadenosine Toxicity in Dividing Human Lymphoblasts.- Inhibition of 3H-Thymidine Incorporation by Adenosine and Deoxyadenosine in Human Peripheral Lymphocytes and Malignant Lymphoid Cell Lines.- S-Adenosylmathionine Metabolism as a Target for Adenosine Toxicity.- Ethanol Induced Nucleotide Catabolism in Mouse T Lympho- blastoid Cells In Vitro.- Increased Level of Ribonucleotide Reductase in Deoxy- adenosine Resistant Adenosine Deaminase Deficient Human Histiocytic Lymphoma Cells.- Inhibition of T Cell Cytotoxicity by Cyclosporine (CSA) Adenosine (ADO), and an Inhibitor of Adenosine Deaminase.- VI. Enzymes.- Mechanism of Urate Production by Guinea-Pig Ileum.- In Vitro Degradation of Pyrimidine Bases: Studies of Rat Liver Dihydropyrimidine Dehydrogenase.- Regulation of Enzymes by Ligand Induced Change in Polymerization.- Synthesis and Turnover of Purine Nucleoside Phosphorylase in Human Lymphocytes.- Reversible Interconversion Between Sulfo and Desulfo Xanthine Dehydrogenase.- Mammalian Mutants Genetically Altered in CTP Synthetase Activity.- Increased Inosinate Dehydrogenase Activity in Mycophenolic Acid Resistant Neuroblastoma Cells.- Murine Lymphocytes and Lymphocyte Lines Secrete Adenosine Deaminase.- Identification of a Purine 5?-Nucleotidase in Human Erythrocytes.- Human Placental Cytoplasmic 5?-Nucleotidase: Kinetics and Molecular Properties.- Regulation of the Cytosol 5?-Nucleotidase of the Heart by Adenylate Energy Charge.- Characterization of Hydroxyurea (HYU) Resistant S49 T Lymphoma Cells.- Purification and Properties of Human Deoxycytidine Kinase.- Purification of Mammalian Glycinamide Ribonucleotide (GAR) Synthetase.- Steady-State Kinetics of the Reaction Catalyzed by GMP Reductase.- Purine De Novo Synthesis and Salvage During Testicular Development in the Rat.- Pathways of Adenine Nucleotide Catabolism in Human Erythrocytes.- Mechanism of Increased Rate of De Novo Purine Biosynthesis in Rat Liver after Bilateral Adrenalectomy.- Increase of Amidophosphoribosyltransferase Activity and Phosphoribosylpyrophosphate Concentration as the Basis for Increased De Novo Purine Biosynthesis in the Regenerating Rat Liver.- Purine Metabolism in Human Neuroblastoma Cell Lines.- Purine Biosynthesis in Chinese Hamster Cell Mutants and Human Fibroblasts Partially Deficient in Adenylo- succinate Lyase.- Purine Synthetic Capacities of De Novo and Salvage Pathways in Rat Hepatoma 3924A Cells.- Metabolism of Purine Nucleotide in the Liver and Kidney of Castrated Rats.- The Hormonal Regulation of Purine Biosynthesis. Control of the Inosinic Acid Branch Point.- VII. purine and Pyrimidine Metabolism during Lymphocyte Differentiation.- Production and Properties of Monoclonal Antibodies Against Human Ecto-5?-Nucleotidase.- AMP-Deaminase and Cytosolic 5?-Nucleotidase in Human and Murine Lymphocyte Subpopulations.- An Explanation for the Heterogeneity in B Lymphocyte Ecto-5?-Nucleotidase Activity in Patients with Hypogammaglobulinemia.- Cell Surface Adenosine Deaminase (ADA) and Its Complexing Protein (ADCP) in Human T-Lymphoid Cells.- On the Role of Cytidine Deaminase in Cellular Metabolism.- Purine Enzyme Activities as Markers of Lymphocytic Differentiation: Studies of Lymphocytes from Horses with Severe Combined Immunodeficiency (SCID).- The Effects of PNP Inhibition on Rat Lymphoid Cell Populations.- Imbalance in Nucleotide Pools of Myeloid Leukemia Cells and HL-60 Cells: Correlation with Cell Cycle Phase, Cell Proliferation and Differentiation.- Enhancement of T Cell Proliferation and Differentiation by 8-Mercaptoguanosine.- Antigen-Specific Enhancement of the Human Antibody Response by a Substituted Nucleoside.- Ectoenzymes of Nucleotide Metabolism on Human Lymphoid Cells.- Separate Mechanisms for Cellular Uptake on Purine Nucleotides by B- and T-Lymphoblasts.- Ecto-5?-Nucleotidase Can Use IMP to Provide the Total Purine Requirements of Mitogen-Stimulated Human T Cells and Human B Lymphoblasts.- VIII. Purine Metabolism in Skeletal Muscle.- Changes of Purine Metabolism During Differentiation of Rat Heart Myoblasts.- Production and Degradation of AMP in Cultured Rat Skeletal and Heart Muscle: A Comparative Study.- Duchenne Muscular Dystrophy: Normal ATP Turnover in Cultured Cells.- Inferences on the Rapid Metabolism of Exogenously Applied ATP in Isolated Smooth Muscle Preparations Using Pharmacological Studies.- Enzyme Activities of Purine Catabolism and Salvage in Human Muscle Tissue.- Purine Salvage in Rat Heart Myoblasts.- Skeletal Muscle Adenosine, Inosine and Hypoxanthine Release Following Ishaemic Forearm Exercise in Myoadenylate Deaminase Deficiency and McArdle?s Disease.- Myoadenylate Deaminase Deficiency: Diagnosis by Forearm Ischemic Exercise Testing.- IX. Purine Nucleotide Metabolism in the Heart.- Purine Nucleotides in Human Hearts During Open Heart Surgery.- X. Purine and Pyrimidine Metabolism in Primary Cell Cultures and in Parasites.- Cell Culture Models for the Study of Purine Metabolism in Human Placental Tissue.- Purine Nucleotide Synthesis in Cultured Rat Embryos Undergoing Organogenesis.- Evidence for a Membrane Adenosine Receptor in LeishmaniaMexicanaMexicana (WR 227).- Adenine Phosphoribosyltransferase-Deficient LeishmaniaDonovani.- 5?-Methylthioadenosine (MTA) Phosphorylase from Promastigotes of Leishmania Donovani.- 6-Thiopurine Riboside Analogs: Their Toxicity and Metabolism in LeishmaniaDonovani and Mammalian Cells.- Purine Salvage Enzymes in Trichomonas Vaginalis.- XI. Nucleoside Kinases and Drug Activation.- Biochemical Basis for Deoxyadenosine and 2-Chlorodeoxy- adenosine Toxicity to Resting Human Lymphocytes.- 2-Chloroadenosine is Phosphorylated and Increases the Production of Hypoxanthine in Human Cells.- Mechanism of Cytotoxicity of 2-Chloro and 2-Bromodeoxy- adenosine for a Human Lymphoblastic Cell Line, CCRF-CEM.- Genetic and Biochemical Characteristics of Three Different Types of Mutants of Mammalian Cells Affected in Adenosine Kinase.- Characterization of Arabinosylguanine Resistance in a Lymphoblastoid Cell Line.- XII. Phosphoribosylpyrophosphate.- The Synthesis of Phosphoribosylpyrophosphate from Glucose Decreases During Amino Acid Starvation of Human Lymphoblasts.- Effect of Fructose on the Concentration of Phosphoribosylpyrophosphate in Isolated Hepatocytes.- The Mechanism of Insulin-Induced Increase of the Rate of De Novo Purine Biosynthesis in Primary Cultured Rat Hypatocytes.- Hormone-Induced Stimulation of Phosphoribosylpyrophosphate and of Purine Synthesis in Mouse Liver In Vivo.- XIII. S-Adenosylmethionine Metabolism.- Cobalamin Inactivation Decreases Purine and Methionine Synthesis in Cultured Human Lymphoblasts.- 5?-Deoxy-5?-Methylthioadenosine Phosphorylase Deficiency in Leukemia: Genetics and Biochemical Aspects.- Metabolism of 5?-Methylthioadenosine in Methionine- Dependent and Methionine-Independent Cells.- Inhibition of De Novo Purine Synthesis by Methylthioadenosine.- Determination of S-Adenosylhomocysteine in Tissues Following Pharmacological Inhibition of S-Adenosylhomocysteine Catabolism.- 4?-Thioadenosine as a Novel Inhibitor of S-Adenosylhomocysteine Hydrolase and an Inducer for the Differentiation of HL-60 Human Cells.- In Vivo Inhibition of Mouse Liver Methyltransferase Enzymes Following Treatment with 2?Deoxycoformycin and 2?Deoxyadenosine.- XIV. Interferon.- Alteration of Ribonucleotide and Deoxyribonucleotide Metabolism by Interferon in Human B-Lymphoblastoid Cells.- Inhibitor of 2/, 5/-01igoadenylate Synthetase Induced in Human T Lymphoblastoid Cell Line Treated with Deoxyadenosine, Deoxycoformycin and Interferon.- 2-5A Synthetase Activities in Herpes Virus Infection and After Interferon Treatment.- Contributors.