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Side-Chain Chemistry of Pteridines
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W. Pfleiderer
© 2019 Walter de Gruyter GmbH, Berlin/Munich/Boston
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Chapters in this book
- Frontmatter I
- Preface V
- Acknowledgments VII
- Contents IX
- How it all Began: A Brief History of the Pteridine Symposia 1
- The Gowland Hopkins Lecture: The Mechanisms of Action of Folate and Pterin Requiring Enzymes 13
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Section A: Chemistry of Pterins and Folates
- Side-Chain Chemistry of Pteridines 31
- A General Method for the Synthesis of 10-Substituted-10-Deaza Folate Analogues 45
- Synthesis and Properties of Pyrimidodiazepines as Ring-Strained Probes of Pterin Utilizing Enzymes 51
- Summary: Pterin and Folate Chemistry 55
- A Facile Method for Preparing 2,4-Diamino-5,8-Dideazapterins 57
- Synthesis of 5,10-Dideaza-5,6,7,8-Tetrahydrofolic Acid (DDATHF) and Analogs 61
- Synthetic Routes to Methotrexate- and Folic Acid-Polyglutamates of High Chemical and Enantiomeric Purity 65
- In Vivo and In Vitro Evaluations of 5-[4-(Substituted Aryl)-1- Piperazinyl]-6-Alkyl-2,4-Pyrimidinediamines as Antitumor Agents 69
- The Electrochemical Oxidation of Tetrahydropterin Derivatives 73
- A Practical Synthesis of (6R)- and (6S)-5,6,7,8-Tetrahydrobiopterins 77
- Chemical Synthesis and Properties of Quinonoid (6R)-Dihydrobiopterin 81
- Pyrazine-Ring Conformations of Tetrahydropterins and Quinonoid-Dihydropterins 85
- Hydrogenation of Silylated Pterins in Benzene Solution 91
- N(5)-Alkylation of Polyacetylated 5,6,7,8-Tetrahydroneopterins 95
- Oxidations Photosensitized by Pterins and Diaminopteridines 99
- Structure of the Riboflavin Synthase/Lumazine Synthase Complex. Arrangement and Chain Folding of Subunits in the Icosahedral Capsid 103
- Use of C18 Silica Cartridges to Purify and Characterize Pterins 107
- Synthesis and Structure-Activity Relationships of Tetrahydrobiopterin Cofactor Analogues 111
- Synthesis, Purification and Properties of a New Class of Pteridine Derivatives 115
- Summary: Chemistry of Pterins 121
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Section B: Biosynthesis and Biochemistry of Pterins
- Biosynthesis of Tetrahydrobiopterin and Related Compounds in Drosophila melanogaster 125
- Tetrahydrobiopterin Biosynthesis in Man 141
- The Biosynthesis of Tetrahydrobiopterin in the Bovine Adrenal Medulla 151
- The Biosynthesis of Tetrahydrobiopterin in Rat Brain 169
- Summary: Biosynthesis of Tetrahydrobiopterin 183
- The Metabolic Role of Tetrahydrobiopterin 185
- Spectroscopic Studies on Tyrosine 3-Monooxygenase from Bovine Adrenal Medulla: A Blue Iron Protein 201
- Queuine-Lacking tNRAs in Relation to the Grade of Malignancy of Specific Tumors, Possible Role of Pteridines 205
- Pteridine Synthesis During Interaction of Interleukin 2 with T Lymphocytes - Modulator Function in IL-2 Signal Transmission 209
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Section C: Biology of Pterins
- Dopamine Neurons in Culture: A Model System for Examination of Neuronal Biopterin Metabolism 215
- Role of the Pituitary in the Regulation of Tetrahydrobiopterin Biosynthesis in the Non-Neuronal Tissues 219
- Distribution of GTP Cyclohydrolase-I, Neopterin, and Biopterin in the Human Brain 223
- Enzymatic Synthesis of 6,7-Dimethyl-8-Ribityllumazine 227
- A Model for Hyperphenylal aninaemia Due to Tetrahydrobiopterin Deficiency 231
- The Effect of Biopterin and its Reduced Derivatives on Cultured Human Lymphocytes 235
- Developmental Aspects of Biopterin Metabolism in Human 239
- Screening for Biopterin Defects Among Hyperphenylalaninemic Patients: Report of a Canadian Program After 3 Years 243
- Need for Therapy in utero of Fetuses with Tetrahydrobiopterin Deficiency 247
- Pteridine Metabolism in Patients Suffering from Amyotrophic Lateral Sclerosis 251
- Urinary Neopterin in Cocaine-Abusing Individuals 257
- Features of Neopterin Determination in Clinical Use 263
- Diurnal Variation in Urinary Pterin Excretion in Man 267
- The Relationship between Pteridines and Colour Dimorphism in the Scorpion Fly 271
- Pteridine Biosynthesis and Manifestation of Pigment Phenotypes in Normal and Neoplastic Cells of Goldfish in Vitro 275
- Light Depending Regulations of Pteridines in the Retina 279
- Differences in the Regulation of Tetrahydrobiopterin Biosynthesis in Neuronal Cells in Culture 283
- NADPH- and NADH-Specific Dihydropteridine Reductase in Teratocarcinoma Cells in Culture: Effect of Nerve Growth Factor Treatment of the Cells on the Enzyme Activities 287
- Reversibility of α-Diketo Reductase Activity by Sepiapterin Reductase 291
- Non-Enzymatic Synthesis of "Drosopterins" from Dihydropterin and 2-Amino-4-0xo-6-Acetyl-3H, 9H-7,8-Dihydropyrimido [4,5b] [1,4]Diazepine 295
- BH4 Biosynthesis: 1H-NMR Evidence for the Pyruvoyl-Tetrahydropterin-Synthase Catalyzed Formation of 6-Pyruvoyl-Tetrahydropterin from Dihydroneopterin Triphosphate 299
- Catabolism of Tetrahydrobiopterin in Man 305
- Pteridine Biosynthesis in Human Amniocytes and Chorionic Villi 309
- The Role of the Kidney in Biopterin Metabolism 315
- Tetrahydrobiopterin-Producing Enzyme Activities in Liver of Animals and Man 319
- Effect of 3-Hydroxykynurenine on GTP Cyclohydrolase Activity and on the Pteridine Pattern in Drosophila melanogaster 323
- Tetrahydrobiopterin Metabolism in Normal Brain, Senile Dementia of the Alzheimer Type and Down's Syndrome 327
- Summary: Biology of Pteridines 331
- Biosynthesis of Pteridines and Metabolism of Aromatic Amino Acids in Drosophila melanogaster 335
- The Inhibition of tRNA Transglycosylases by Pteridines as a Mean for Metabolic Control of Gene Expression 339
- Modulation of Dopamine Synthesis by Nerve Terminal Autoreceptors: A Role for Tetrahydrobiopterin? 347
- A Monoclonal Antibody Reacting with All Three Aromatic Amino Acid Hydroxylases 351
- Alterations in Cofactor-Dependent Activity of Phenylalanine Hydroxylase as a Function of pH 355
- Interaction of a Monoclonal Antibody with Rat Liver Phenylalanine Hydroxylase 359
- The Effect of Dietary Iron on the Activity of Rat Liver Phenylalanine Hydroxylase 363
- Strict Requirement of Fe2+ for Tryptophan 5-Monooxygenase from Mouse Mastocytoma, P-815 369
- Tetrahydrobiopterin and the Regulation of Catecholamine Synthesis in Bovine Adrenal Medullary Chromaffin Cells 373
- Cofactor Activity of Tetrahydropterins for Tyrosine Hydroxylation in PC12 Pheochromocytoma Cells 377
- Summary: Pterin-Dependent Biological Reactions 381
- Tetrahydrobiopterin Deficiency. Analysis from an International Survey 385
- Cofactor Specificity of 6,6-Disubstituted Tetrahydropterins, and their Potential in the Treatment of Neurological Disorders 391
- Normal Concentrations of Tetrahydrobiopterin in the Cerebrospinal Fluid of Patients with Dihydropteridine Reductase Deficiency 395
- Prenatal Diagnosis of Tetrahydrobiopterin Deficiency 399
- Defective Biopterin Biosynthesis in a Chinese Infant 403
- Correlation of Dihydropterine Reductase Cross Reacting Material with Non-Responsiveness to a Tetrahydrobiopterin Load 407
- Neopterin and Dihydroneopterins in Serum of Controls and Patients with Various Diseases. Circadian Rhythm of Neopterin. Influence of Cortisol? 411
- Neopterin Content and GTP-Cyclohydrolase Activity of Blood Cells of Controls and Patients Positive for LAV/HTLV-III Antibodies 415
- Neopterin in Bone Marrow Transplant Monitoring: An Improvement in its Use for GVHD Diagnosis 419
- Importance of Neopterin Determination in Individuals at Risk for AIDS 427
- Biochemical Aspects of Pteridines During Interaction Between Activated T-Lymphocytes and Monocytes/Macrophages in Patients 431
- Summary: Pterins and Human Illness 443
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Section D: Folates and Pterins in Mammalian Tissues
- Folates in Tissues and Cells. Support for a "Two-Tier" Hypothesis of Regulation of One-Carbon Metabolism 447
- Elevation in the Rate of Cellular Folate Catabolism in Mid-Pregnancy in the Rat 467
- The Red Blood Cell as a Storage Site for Folic Acid 471
- Methotrexate and Biopterin Levels in Blood Following Low Dose Administration for Psoriasis 475
- Summary: Folates in Tissue and Cells 479
- Folate Rescue of N2O-Induced Inhibition in Murine Lymphocytes 481
- Folate Absorption and Metabolism in Alcohol Fed Rats 485
- Chronic and Acute Effects of Ethanol on Renal Clearance and Urinary Excretion of Folate in Rats 489
- Effect of Chronic Anticonvulsant Treatment on Folate Concentrations in the Rat 495
- Alcohol Induced Methyl Group Wastage as a Possible Cause of Fatty Liver 505
- Folate Catabolism in the Syrian Golden Hamster 509
- The Level of Folate Catabolism in Normal Human Populations, Suggesting that the Current Level of RDA for Folate is Excessive 513
- Microdetermination of Folate Monoglutamates in Serum by High-Performance Liquid Chromatography with Electrochemical Detection 517
- Folate Status in Psychiatric Patients: Relationship with CSF Neurotransmitter Metabolites 523
- Folate, Thiamine and Vitamin B12 Levels in Outpatient Epileptics 527
- Effect of Aspirin Ingestion on Folate Bioavailability Evaluated by Rat Liver Bioassay 531
- Brush Border Pteroylpolyglutamate Hydrolase in Pig Jejunum 539
- Use of CI-920 in the Characterization of the Methotrexate Transport Defect in a Resistant Human Leukemic CCRF-CEM Cell Line 543
- The Effect of Oxidative Stress on Methotrexate (MTX) Transport by Rat Hepatocytes 547
- Folate Transport by Pig Intestinal Brush Border Vesicles 551
- Depressed Folate Transfer Across the Mammary Gland Secondary to Iron Deficiency in the Rat 555
- Studies on the Mechanism of Folate Transport in Isolated Hepatocytes 559
- Analysis of the pH and Na+ Dependence of Intestinal Folate Transport 563
- Intestinal Transport of Folate. Characterization of the Transport Events at the Brush Border and the Basolateral Membranes 567
- The Synthesis of Some Novel Probes of Folate Transport and Binding 571
- Photoaffinity Probes of Dihydrofolate Reductase and of the Membrane Carrier for Folate Analogues 575
- The Use of Biosynthetic Radioactive Folylpolyglutamates to Study Intestinal Digestion and Absorption of Folate 579
- Selective Inhibition of Bacterial Carboxypeptidase G and Pancreatic Conjugase by 2-Mercaptomethylglutaric Acid 583
- Summary: Folate Absorption and Transport 587
- Studies on Glycine-N-Methyltransferase 593
- Folate Binding Protein from Pediococcus Cerevisiae Strains Possessing Active Transport Systems for Folates 597
- Immobilized Folate Binding Protein from Cow's Milk Used for Quantitation of Folate 603
- Characterization of Rabbit Antibodies Against the Folate Binding Protein from Cow's Milk 607
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Section E: Enzymology of Folates
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1. Thymidylate Synthase
- Genetic and Chemical Studies on Thymidylate Synthase 613
- Active Site Probes of Thymidylate Synthetase 631
- Resonance-Raman Spectroscopic Identification of the Transient Intermediates Formed in the Native Ternary Complex with Thymidylate Synthase 639
- The Reversal of the Cytotoxicity of Folate-Based Thymidylate Synthase Inhibitors in Cultures L1210 Cells 645
- Thymidylate Synthase Activity in the Tapeworm, Hymenolepis diminuta 651
- Identification of Poly G Bound to Thymidylate Synthase 655
- Methotrexate Derivates of Deoxyuridylate Showing Inhibitory Properties for Thymidylate Synthetase from Lactobacillus casei 659
- Comparison of Thymidylate Synthase Isolated from Mouse Normal and Tumour Tissues 663
- Thymidylate Synthase Interaction with Analogues of dUMP and 5-Fluorid- 2'-Deoxyuridine-5'-Phosphate with Modified Phosphate Groups 667
- An In Vitro System for Studies on Inhibition of the Thymidylate Cycle 671
- N10-Propargyl-5,8-Dideazafolic Acid Polyglutamates as Inhibitors of Thymidylate Synthase and their Intracellular Formation 675
- Sequential CMF in Metastatic Breast Cancer: An Attempt to Increase Effectiveness by Means of Biochemical Modulation 681
- Model Studies of Thymidylate Synthase Reaction 687
- Synergistic Interaction Between Folinic Acid and the Fluoropyrimidines 691
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2. Methionine Biosynthesis
- Methionine Biosynthesis 697
- Impaired Formylation and Uptake of Tetrahydrofolate by Rat Small Gut Following Cobalamin Inactivation 709
- Heterogeneity in Functional Methionine Synthase Deficiency 713
- Summary: Methionine Biosynthesis 717
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3. Folyl Polyglutamate Synthetase
- Folylpoly-γ-glutamate Synthetase 719
- Cytotoxic Effects and Inhibition of Folylpolyglutamate Synthetase by Folate Analogs Containing 2, Omega-Diaminoalkanoic Acids 729
- An Upstream Gene Regulates the Expression of Folylpolyglutamate Synthetase-Dihydrofolate Synthetase in Escherichia coli 733
- Occurence and Synthesis of Pteroyl-γ-glutamyl-γ-glutamyl-poly-α-glutamates in Escherichia coli 737
- Summary: Folylpolyglutamate Synthesis 741
- The Metabolism of Pteroylpolyglutamates 743
- Dihydropteroyl Hexaglutamate and T4 Phage Baseplate Assembly 757
- Effects of Polyglutamylation on Folate Cofactor and Antifolate Activity in the Thymidylate Synthase Cycle of Permeabilized Murine Leukemia L1210 Cells 763
- Summary: Pteroylpolyglutamate metabolism 767
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4. Dihydrofolate Reductase
- Recent Advances in the Study of Dihydrofolate Reductase 769
- The 2.8 Å Structure of a Type II Plasmid Encoded Dihydrofolate Reductase 789
- Mutations in the Human Dihydrofolate Reductase 793
- Theoretical Studies of the Structure, Conformational and Electronic Properties of Anticancer Folate Inhibitors 799
- Binding of Inhibitors with Spin-Labeled Side Chains to Dihydrofolate Reductase (DHFR) from Several Species 803
- Affinity Labeling of Dihydrofolate Reductase with an Iodoacetyl Lysine Analogue of Methotrexate 807
- Escherichia coli Dihydrofolate Reductase Isolated as a Folate Complex 811
- Dihydrofolate Reductase from Soybean Seedlings 815
- Use of Antibodies as Structural Probes of Dihydrofolate Reductases and Enzyme-Ligand Complexes 819
- Cooperativity in Inhibitor Binding to Neisseria gonorrhoeae Dihydrofolate Reductase 823
- pH Studies of the Reaction Catalyzed by Dihydrofolate Reductase from E. coli 827
- Effects of pH on Reactions Catalyzed by Dihydrofolate Reductase from Chicken Liver 831
- Unconjugated Dihydropterin Substrates for Bovine Liver Dihydrofolate Reductase 835
- Enzymatic Characterization of Recombinant Human Dihydrofolate Reductase Produced in E. coli 839
- Levels of Folates and Methotrexate Polyglutamate Formation in Chinese Hamster Ovary Cells Lacking Dihydrofolate Reductase 843
- Methotrexate in Adjuvant Arthritis 847
- Computer Graphic Modeling in Drug Design: Conformational Analysis and Active-Site Modeling of Lipophilic Diaminopyrimidines 851
- Effect of Antifolates 10-Methyl- and 10-Ethyl-10-Deaza-Aminopterin on a Human Breast Cancer Cell Line 855
- Biochemical and Cytotoxic Effects of the Erythro- and Threo-Isomers of Gamma-Fluoro-Methotrexate 861
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5. Other Folate Enzymes
- C1-Tetrahydrofolate-Synthase, a Multifunctional Enzyme Involved in Purine Metabolism, and its Related Monofunctional Enzymes 865
- The Interaction of Tetrahydropteroylpolyglutamates with 10-Formyltetra-Hydrofolate Synthetase 887
- Summary: Folates in C 1 Metabolism 891
- Chemical Aspects of Dimethylglycine Dehydrogenase and Sarcosine Dehydrogenase 893
- Folate Normalizes Elevated PRPP Levels of Folate-Deficient HL-60 Cells 897
- Stereochemistry of Hydride Transfer to NADP+ by Methylene Tetrahydrofolate Dehydrogenase from Pig Liver 901
- The Effects of Thyroxine Status on Hepatic Levels of 10-Formyltetrahydrofolic Acid: NADP Oxidoreductase 905
- Interaction of Homocysteine with Methionine Synthetase 909
- Minor Form of Human Hepatic Betaine: Homocysteine S-Methyltransferase 913
- Studies of Cobalamin-Dependent Methionine Synthase from Escherichia coli B 917
- Inhibition of Methylenetetrahydrofolate Reductase by Adenosyl Methionine 921
- Regulation of Folate Homeostasis 925
- An Endogenous Inhibitor of Neurospora Folylpolyglutamate Synthetase 929
- Folylpolyglutamate Hydrolase from Beef Liver 933
- Use of Mammalian Cell Transformation to Isolate Genomic Sequences Encoding Human Folylpolyglutamate Synthetase (FPGS) and Dihydrofolate Reductase (DHFR) 937
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Section F: Methotrexate and Other Anti-Folates
- Antifolates: Expanding Horizons in 1986 945
- Deaza Derivatives of Tetrahydrofolic Acid. A New Class of Folate Antimetabolite 953
- Structure Activity Relationships of Novel Triazine Antifolates 959
- The Effect of 7-Hydroxymethotrexate on the Antitumor Activity and Host Toxicity of Methotrexate In Vivo 963
- Summary: The Biology of Antifolates 967
- Crystal Structure of Methotrexate and its Conformational Comparison with Related Structures 969
- Effect of Methotrexate on Reduced Folates and Thymidylate Synthesis During Growth of L1210 Cells 973
- Dihydrofolate Reductase from Human Osteosarcoma Cells Resistant to Methotrexate 977
- Evidence for Direct Inhibition of Metabolic Pathways as a Mechanism of Action of Methotrexate 981
- Inhibition of Dihydrofolate Reductase and Thymidylate Synthase by Methotrexate Polyglutamate Analogues Lacking "Internal" α-Carboxyl Groups 985
- The Antifolate Activity of Poly-γ-Glutamyl Derivatives of Methotrexate, 10-Deazaaminopterin and 10-Ethyl-10 Deazaaminopterin 989
- Polyglutamation of the Thymidylate Synthase Inhibitor, N10-Propargyl-5,8-Dideazafolic Acid (CB 3717), in Organs of Ehrlich Ascites Carcinoma-Bearing Mice 993
- 5,8-Dideazafolates as Substrates for Folypoly-γ-Glutamate Synthetase from Pig Liver 997
- 5-Substituted-5-Deaza Analogues of Classical Antifolates 1001
- Azido-Substituted Antifolate Drugs: Synthesis, Structure, and Activity 1005
- Summary: Novel Antifolates 1009
- Author Index 1011
- Subject Index 1017
- List of Participants 1033
- Backmatter 1051
Chapters in this book
- Frontmatter I
- Preface V
- Acknowledgments VII
- Contents IX
- How it all Began: A Brief History of the Pteridine Symposia 1
- The Gowland Hopkins Lecture: The Mechanisms of Action of Folate and Pterin Requiring Enzymes 13
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Section A: Chemistry of Pterins and Folates
- Side-Chain Chemistry of Pteridines 31
- A General Method for the Synthesis of 10-Substituted-10-Deaza Folate Analogues 45
- Synthesis and Properties of Pyrimidodiazepines as Ring-Strained Probes of Pterin Utilizing Enzymes 51
- Summary: Pterin and Folate Chemistry 55
- A Facile Method for Preparing 2,4-Diamino-5,8-Dideazapterins 57
- Synthesis of 5,10-Dideaza-5,6,7,8-Tetrahydrofolic Acid (DDATHF) and Analogs 61
- Synthetic Routes to Methotrexate- and Folic Acid-Polyglutamates of High Chemical and Enantiomeric Purity 65
- In Vivo and In Vitro Evaluations of 5-[4-(Substituted Aryl)-1- Piperazinyl]-6-Alkyl-2,4-Pyrimidinediamines as Antitumor Agents 69
- The Electrochemical Oxidation of Tetrahydropterin Derivatives 73
- A Practical Synthesis of (6R)- and (6S)-5,6,7,8-Tetrahydrobiopterins 77
- Chemical Synthesis and Properties of Quinonoid (6R)-Dihydrobiopterin 81
- Pyrazine-Ring Conformations of Tetrahydropterins and Quinonoid-Dihydropterins 85
- Hydrogenation of Silylated Pterins in Benzene Solution 91
- N(5)-Alkylation of Polyacetylated 5,6,7,8-Tetrahydroneopterins 95
- Oxidations Photosensitized by Pterins and Diaminopteridines 99
- Structure of the Riboflavin Synthase/Lumazine Synthase Complex. Arrangement and Chain Folding of Subunits in the Icosahedral Capsid 103
- Use of C18 Silica Cartridges to Purify and Characterize Pterins 107
- Synthesis and Structure-Activity Relationships of Tetrahydrobiopterin Cofactor Analogues 111
- Synthesis, Purification and Properties of a New Class of Pteridine Derivatives 115
- Summary: Chemistry of Pterins 121
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Section B: Biosynthesis and Biochemistry of Pterins
- Biosynthesis of Tetrahydrobiopterin and Related Compounds in Drosophila melanogaster 125
- Tetrahydrobiopterin Biosynthesis in Man 141
- The Biosynthesis of Tetrahydrobiopterin in the Bovine Adrenal Medulla 151
- The Biosynthesis of Tetrahydrobiopterin in Rat Brain 169
- Summary: Biosynthesis of Tetrahydrobiopterin 183
- The Metabolic Role of Tetrahydrobiopterin 185
- Spectroscopic Studies on Tyrosine 3-Monooxygenase from Bovine Adrenal Medulla: A Blue Iron Protein 201
- Queuine-Lacking tNRAs in Relation to the Grade of Malignancy of Specific Tumors, Possible Role of Pteridines 205
- Pteridine Synthesis During Interaction of Interleukin 2 with T Lymphocytes - Modulator Function in IL-2 Signal Transmission 209
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Section C: Biology of Pterins
- Dopamine Neurons in Culture: A Model System for Examination of Neuronal Biopterin Metabolism 215
- Role of the Pituitary in the Regulation of Tetrahydrobiopterin Biosynthesis in the Non-Neuronal Tissues 219
- Distribution of GTP Cyclohydrolase-I, Neopterin, and Biopterin in the Human Brain 223
- Enzymatic Synthesis of 6,7-Dimethyl-8-Ribityllumazine 227
- A Model for Hyperphenylal aninaemia Due to Tetrahydrobiopterin Deficiency 231
- The Effect of Biopterin and its Reduced Derivatives on Cultured Human Lymphocytes 235
- Developmental Aspects of Biopterin Metabolism in Human 239
- Screening for Biopterin Defects Among Hyperphenylalaninemic Patients: Report of a Canadian Program After 3 Years 243
- Need for Therapy in utero of Fetuses with Tetrahydrobiopterin Deficiency 247
- Pteridine Metabolism in Patients Suffering from Amyotrophic Lateral Sclerosis 251
- Urinary Neopterin in Cocaine-Abusing Individuals 257
- Features of Neopterin Determination in Clinical Use 263
- Diurnal Variation in Urinary Pterin Excretion in Man 267
- The Relationship between Pteridines and Colour Dimorphism in the Scorpion Fly 271
- Pteridine Biosynthesis and Manifestation of Pigment Phenotypes in Normal and Neoplastic Cells of Goldfish in Vitro 275
- Light Depending Regulations of Pteridines in the Retina 279
- Differences in the Regulation of Tetrahydrobiopterin Biosynthesis in Neuronal Cells in Culture 283
- NADPH- and NADH-Specific Dihydropteridine Reductase in Teratocarcinoma Cells in Culture: Effect of Nerve Growth Factor Treatment of the Cells on the Enzyme Activities 287
- Reversibility of α-Diketo Reductase Activity by Sepiapterin Reductase 291
- Non-Enzymatic Synthesis of "Drosopterins" from Dihydropterin and 2-Amino-4-0xo-6-Acetyl-3H, 9H-7,8-Dihydropyrimido [4,5b] [1,4]Diazepine 295
- BH4 Biosynthesis: 1H-NMR Evidence for the Pyruvoyl-Tetrahydropterin-Synthase Catalyzed Formation of 6-Pyruvoyl-Tetrahydropterin from Dihydroneopterin Triphosphate 299
- Catabolism of Tetrahydrobiopterin in Man 305
- Pteridine Biosynthesis in Human Amniocytes and Chorionic Villi 309
- The Role of the Kidney in Biopterin Metabolism 315
- Tetrahydrobiopterin-Producing Enzyme Activities in Liver of Animals and Man 319
- Effect of 3-Hydroxykynurenine on GTP Cyclohydrolase Activity and on the Pteridine Pattern in Drosophila melanogaster 323
- Tetrahydrobiopterin Metabolism in Normal Brain, Senile Dementia of the Alzheimer Type and Down's Syndrome 327
- Summary: Biology of Pteridines 331
- Biosynthesis of Pteridines and Metabolism of Aromatic Amino Acids in Drosophila melanogaster 335
- The Inhibition of tRNA Transglycosylases by Pteridines as a Mean for Metabolic Control of Gene Expression 339
- Modulation of Dopamine Synthesis by Nerve Terminal Autoreceptors: A Role for Tetrahydrobiopterin? 347
- A Monoclonal Antibody Reacting with All Three Aromatic Amino Acid Hydroxylases 351
- Alterations in Cofactor-Dependent Activity of Phenylalanine Hydroxylase as a Function of pH 355
- Interaction of a Monoclonal Antibody with Rat Liver Phenylalanine Hydroxylase 359
- The Effect of Dietary Iron on the Activity of Rat Liver Phenylalanine Hydroxylase 363
- Strict Requirement of Fe2+ for Tryptophan 5-Monooxygenase from Mouse Mastocytoma, P-815 369
- Tetrahydrobiopterin and the Regulation of Catecholamine Synthesis in Bovine Adrenal Medullary Chromaffin Cells 373
- Cofactor Activity of Tetrahydropterins for Tyrosine Hydroxylation in PC12 Pheochromocytoma Cells 377
- Summary: Pterin-Dependent Biological Reactions 381
- Tetrahydrobiopterin Deficiency. Analysis from an International Survey 385
- Cofactor Specificity of 6,6-Disubstituted Tetrahydropterins, and their Potential in the Treatment of Neurological Disorders 391
- Normal Concentrations of Tetrahydrobiopterin in the Cerebrospinal Fluid of Patients with Dihydropteridine Reductase Deficiency 395
- Prenatal Diagnosis of Tetrahydrobiopterin Deficiency 399
- Defective Biopterin Biosynthesis in a Chinese Infant 403
- Correlation of Dihydropterine Reductase Cross Reacting Material with Non-Responsiveness to a Tetrahydrobiopterin Load 407
- Neopterin and Dihydroneopterins in Serum of Controls and Patients with Various Diseases. Circadian Rhythm of Neopterin. Influence of Cortisol? 411
- Neopterin Content and GTP-Cyclohydrolase Activity of Blood Cells of Controls and Patients Positive for LAV/HTLV-III Antibodies 415
- Neopterin in Bone Marrow Transplant Monitoring: An Improvement in its Use for GVHD Diagnosis 419
- Importance of Neopterin Determination in Individuals at Risk for AIDS 427
- Biochemical Aspects of Pteridines During Interaction Between Activated T-Lymphocytes and Monocytes/Macrophages in Patients 431
- Summary: Pterins and Human Illness 443
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Section D: Folates and Pterins in Mammalian Tissues
- Folates in Tissues and Cells. Support for a "Two-Tier" Hypothesis of Regulation of One-Carbon Metabolism 447
- Elevation in the Rate of Cellular Folate Catabolism in Mid-Pregnancy in the Rat 467
- The Red Blood Cell as a Storage Site for Folic Acid 471
- Methotrexate and Biopterin Levels in Blood Following Low Dose Administration for Psoriasis 475
- Summary: Folates in Tissue and Cells 479
- Folate Rescue of N2O-Induced Inhibition in Murine Lymphocytes 481
- Folate Absorption and Metabolism in Alcohol Fed Rats 485
- Chronic and Acute Effects of Ethanol on Renal Clearance and Urinary Excretion of Folate in Rats 489
- Effect of Chronic Anticonvulsant Treatment on Folate Concentrations in the Rat 495
- Alcohol Induced Methyl Group Wastage as a Possible Cause of Fatty Liver 505
- Folate Catabolism in the Syrian Golden Hamster 509
- The Level of Folate Catabolism in Normal Human Populations, Suggesting that the Current Level of RDA for Folate is Excessive 513
- Microdetermination of Folate Monoglutamates in Serum by High-Performance Liquid Chromatography with Electrochemical Detection 517
- Folate Status in Psychiatric Patients: Relationship with CSF Neurotransmitter Metabolites 523
- Folate, Thiamine and Vitamin B12 Levels in Outpatient Epileptics 527
- Effect of Aspirin Ingestion on Folate Bioavailability Evaluated by Rat Liver Bioassay 531
- Brush Border Pteroylpolyglutamate Hydrolase in Pig Jejunum 539
- Use of CI-920 in the Characterization of the Methotrexate Transport Defect in a Resistant Human Leukemic CCRF-CEM Cell Line 543
- The Effect of Oxidative Stress on Methotrexate (MTX) Transport by Rat Hepatocytes 547
- Folate Transport by Pig Intestinal Brush Border Vesicles 551
- Depressed Folate Transfer Across the Mammary Gland Secondary to Iron Deficiency in the Rat 555
- Studies on the Mechanism of Folate Transport in Isolated Hepatocytes 559
- Analysis of the pH and Na+ Dependence of Intestinal Folate Transport 563
- Intestinal Transport of Folate. Characterization of the Transport Events at the Brush Border and the Basolateral Membranes 567
- The Synthesis of Some Novel Probes of Folate Transport and Binding 571
- Photoaffinity Probes of Dihydrofolate Reductase and of the Membrane Carrier for Folate Analogues 575
- The Use of Biosynthetic Radioactive Folylpolyglutamates to Study Intestinal Digestion and Absorption of Folate 579
- Selective Inhibition of Bacterial Carboxypeptidase G and Pancreatic Conjugase by 2-Mercaptomethylglutaric Acid 583
- Summary: Folate Absorption and Transport 587
- Studies on Glycine-N-Methyltransferase 593
- Folate Binding Protein from Pediococcus Cerevisiae Strains Possessing Active Transport Systems for Folates 597
- Immobilized Folate Binding Protein from Cow's Milk Used for Quantitation of Folate 603
- Characterization of Rabbit Antibodies Against the Folate Binding Protein from Cow's Milk 607
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Section E: Enzymology of Folates
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1. Thymidylate Synthase
- Genetic and Chemical Studies on Thymidylate Synthase 613
- Active Site Probes of Thymidylate Synthetase 631
- Resonance-Raman Spectroscopic Identification of the Transient Intermediates Formed in the Native Ternary Complex with Thymidylate Synthase 639
- The Reversal of the Cytotoxicity of Folate-Based Thymidylate Synthase Inhibitors in Cultures L1210 Cells 645
- Thymidylate Synthase Activity in the Tapeworm, Hymenolepis diminuta 651
- Identification of Poly G Bound to Thymidylate Synthase 655
- Methotrexate Derivates of Deoxyuridylate Showing Inhibitory Properties for Thymidylate Synthetase from Lactobacillus casei 659
- Comparison of Thymidylate Synthase Isolated from Mouse Normal and Tumour Tissues 663
- Thymidylate Synthase Interaction with Analogues of dUMP and 5-Fluorid- 2'-Deoxyuridine-5'-Phosphate with Modified Phosphate Groups 667
- An In Vitro System for Studies on Inhibition of the Thymidylate Cycle 671
- N10-Propargyl-5,8-Dideazafolic Acid Polyglutamates as Inhibitors of Thymidylate Synthase and their Intracellular Formation 675
- Sequential CMF in Metastatic Breast Cancer: An Attempt to Increase Effectiveness by Means of Biochemical Modulation 681
- Model Studies of Thymidylate Synthase Reaction 687
- Synergistic Interaction Between Folinic Acid and the Fluoropyrimidines 691
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2. Methionine Biosynthesis
- Methionine Biosynthesis 697
- Impaired Formylation and Uptake of Tetrahydrofolate by Rat Small Gut Following Cobalamin Inactivation 709
- Heterogeneity in Functional Methionine Synthase Deficiency 713
- Summary: Methionine Biosynthesis 717
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3. Folyl Polyglutamate Synthetase
- Folylpoly-γ-glutamate Synthetase 719
- Cytotoxic Effects and Inhibition of Folylpolyglutamate Synthetase by Folate Analogs Containing 2, Omega-Diaminoalkanoic Acids 729
- An Upstream Gene Regulates the Expression of Folylpolyglutamate Synthetase-Dihydrofolate Synthetase in Escherichia coli 733
- Occurence and Synthesis of Pteroyl-γ-glutamyl-γ-glutamyl-poly-α-glutamates in Escherichia coli 737
- Summary: Folylpolyglutamate Synthesis 741
- The Metabolism of Pteroylpolyglutamates 743
- Dihydropteroyl Hexaglutamate and T4 Phage Baseplate Assembly 757
- Effects of Polyglutamylation on Folate Cofactor and Antifolate Activity in the Thymidylate Synthase Cycle of Permeabilized Murine Leukemia L1210 Cells 763
- Summary: Pteroylpolyglutamate metabolism 767
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4. Dihydrofolate Reductase
- Recent Advances in the Study of Dihydrofolate Reductase 769
- The 2.8 Å Structure of a Type II Plasmid Encoded Dihydrofolate Reductase 789
- Mutations in the Human Dihydrofolate Reductase 793
- Theoretical Studies of the Structure, Conformational and Electronic Properties of Anticancer Folate Inhibitors 799
- Binding of Inhibitors with Spin-Labeled Side Chains to Dihydrofolate Reductase (DHFR) from Several Species 803
- Affinity Labeling of Dihydrofolate Reductase with an Iodoacetyl Lysine Analogue of Methotrexate 807
- Escherichia coli Dihydrofolate Reductase Isolated as a Folate Complex 811
- Dihydrofolate Reductase from Soybean Seedlings 815
- Use of Antibodies as Structural Probes of Dihydrofolate Reductases and Enzyme-Ligand Complexes 819
- Cooperativity in Inhibitor Binding to Neisseria gonorrhoeae Dihydrofolate Reductase 823
- pH Studies of the Reaction Catalyzed by Dihydrofolate Reductase from E. coli 827
- Effects of pH on Reactions Catalyzed by Dihydrofolate Reductase from Chicken Liver 831
- Unconjugated Dihydropterin Substrates for Bovine Liver Dihydrofolate Reductase 835
- Enzymatic Characterization of Recombinant Human Dihydrofolate Reductase Produced in E. coli 839
- Levels of Folates and Methotrexate Polyglutamate Formation in Chinese Hamster Ovary Cells Lacking Dihydrofolate Reductase 843
- Methotrexate in Adjuvant Arthritis 847
- Computer Graphic Modeling in Drug Design: Conformational Analysis and Active-Site Modeling of Lipophilic Diaminopyrimidines 851
- Effect of Antifolates 10-Methyl- and 10-Ethyl-10-Deaza-Aminopterin on a Human Breast Cancer Cell Line 855
- Biochemical and Cytotoxic Effects of the Erythro- and Threo-Isomers of Gamma-Fluoro-Methotrexate 861
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5. Other Folate Enzymes
- C1-Tetrahydrofolate-Synthase, a Multifunctional Enzyme Involved in Purine Metabolism, and its Related Monofunctional Enzymes 865
- The Interaction of Tetrahydropteroylpolyglutamates with 10-Formyltetra-Hydrofolate Synthetase 887
- Summary: Folates in C 1 Metabolism 891
- Chemical Aspects of Dimethylglycine Dehydrogenase and Sarcosine Dehydrogenase 893
- Folate Normalizes Elevated PRPP Levels of Folate-Deficient HL-60 Cells 897
- Stereochemistry of Hydride Transfer to NADP+ by Methylene Tetrahydrofolate Dehydrogenase from Pig Liver 901
- The Effects of Thyroxine Status on Hepatic Levels of 10-Formyltetrahydrofolic Acid: NADP Oxidoreductase 905
- Interaction of Homocysteine with Methionine Synthetase 909
- Minor Form of Human Hepatic Betaine: Homocysteine S-Methyltransferase 913
- Studies of Cobalamin-Dependent Methionine Synthase from Escherichia coli B 917
- Inhibition of Methylenetetrahydrofolate Reductase by Adenosyl Methionine 921
- Regulation of Folate Homeostasis 925
- An Endogenous Inhibitor of Neurospora Folylpolyglutamate Synthetase 929
- Folylpolyglutamate Hydrolase from Beef Liver 933
- Use of Mammalian Cell Transformation to Isolate Genomic Sequences Encoding Human Folylpolyglutamate Synthetase (FPGS) and Dihydrofolate Reductase (DHFR) 937
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Section F: Methotrexate and Other Anti-Folates
- Antifolates: Expanding Horizons in 1986 945
- Deaza Derivatives of Tetrahydrofolic Acid. A New Class of Folate Antimetabolite 953
- Structure Activity Relationships of Novel Triazine Antifolates 959
- The Effect of 7-Hydroxymethotrexate on the Antitumor Activity and Host Toxicity of Methotrexate In Vivo 963
- Summary: The Biology of Antifolates 967
- Crystal Structure of Methotrexate and its Conformational Comparison with Related Structures 969
- Effect of Methotrexate on Reduced Folates and Thymidylate Synthesis During Growth of L1210 Cells 973
- Dihydrofolate Reductase from Human Osteosarcoma Cells Resistant to Methotrexate 977
- Evidence for Direct Inhibition of Metabolic Pathways as a Mechanism of Action of Methotrexate 981
- Inhibition of Dihydrofolate Reductase and Thymidylate Synthase by Methotrexate Polyglutamate Analogues Lacking "Internal" α-Carboxyl Groups 985
- The Antifolate Activity of Poly-γ-Glutamyl Derivatives of Methotrexate, 10-Deazaaminopterin and 10-Ethyl-10 Deazaaminopterin 989
- Polyglutamation of the Thymidylate Synthase Inhibitor, N10-Propargyl-5,8-Dideazafolic Acid (CB 3717), in Organs of Ehrlich Ascites Carcinoma-Bearing Mice 993
- 5,8-Dideazafolates as Substrates for Folypoly-γ-Glutamate Synthetase from Pig Liver 997
- 5-Substituted-5-Deaza Analogues of Classical Antifolates 1001
- Azido-Substituted Antifolate Drugs: Synthesis, Structure, and Activity 1005
- Summary: Novel Antifolates 1009
- Author Index 1011
- Subject Index 1017
- List of Participants 1033
- Backmatter 1051