Radioimmunoassay for Neopterin in Body Fluid and Tissues

Chapters in this book

1. Frontmatter I
2. Preface V
3. ACKNOWLEDGEMENTS VII
4. PARTICIPANTS IX
5. Contents XIII
6. The Gowland Hopkins Lecture: Transport of Folate and Pterin Compounds 1
7. Chemical Aspects (1)
8. Scottish International Education Trust Lecture: Synthetic Methods in Pteridine Chemistry: Some Applications to Pteridine Natural Products 23
9. Synthesis, Chemical and Enzymatic Properties, and Therapeutic Potential of 6,6-Disubstituted Tetrahydroand Quinoid-Dihydro-Pterins 51
10. The Structure of Quinonoid Dihydropterins [2-Amino-7,8(6H)-Dihydropteridin-4-ones] 57
11. Some Simple s-Triazolopteridines 63
12. Linear Tricyclic Analogs of Pteridines 69
13. Reactions of Furazano [3,4-djPyrimidines and their Application to Pteridine Synthesis 73
14. Syntheses of some Blocked 7,8-Dihydropteridines 79
15. Synthesis of Chiral Reduced Pteridine Coenzymes 85
16. Report on Discussions 91
17. Chemical Aspects (2)
18. Reactivity of Pteridines 93
19. Synthesis and Antitumor Activity of 10-Deazaminopterins 109
20. Synthesis and Biological Activity of 5-Deazafolic Acid and 5-Deazaaminopterin 115
21. The Nor-Analogues of Folic Acid 121
22. Report on Discussions 127
23. Neurochemical and Clinical Aspects
24. Metabolism of Pteridine Cofactors in Neurochemistry 131
25. Pteridines in Cancer and Other Diseases 153
26. Dihydropteridine Reductase Activity in Human Breast Cancer. Studies of 580 Cases and Correlations with Hormone Receptors and Cellular Typing 159
27. A Critical Appraisal of Methods for the Quantitative Analysis of Tetrahydrobiopterin, Dihydrobiopterin and Biopterin in Human Urine, Serum and CSE 165
28. Inhibition of Pterin Biosynthesis in the Adrenergic Neuroblastoma N1E115 by Tetrahydrobiopterin and Folate 171
29. Penetration of Reduced Pterins into Rat Brain: Effect on Biogenic Amine Synthesis 177
30. Neopterin Deficiency (GTP Cyclohydrolase I Deficiency), a New Variant of Hyperphenylalaninemia 183
31. Folate Pathways in Cells from Fragile X Syndrome Patients and Carriers 189
32. Report on Discussions 195
33. Enzymology
34. The Interaction of Substrates and Inhibitors with Dihydrofolate Reductase 197
35. Catalytic Site of Dihydrofolate Reductase 215
36. Structure, Function and Affinity Labelling Studies of Dihydrofolate Reductase 223
37. Methylene Tetrahydrofoíate Reductase: Studies in a Human Mutant and Mammalian Liver 229
38. Studies on Methylenetetrahydrofolate Reductase from Pig Liver: Catalytic Mechanism and Regulation by Adenosylmethionine 235
39. Role of Methylenetetrahydrofolic Acid Reductase in Regulation of Folic Acid Metabolism and its Relation to the Methyl Trap Hypothesis 241
40. The Mechanism of Action of the Transformylase Enzymes 247
41. Folypolyglutamate Synthesis in Neurospora Crassa 251
42. Report on Discussions 257
43. Clinical Aspects: Cancer
44. Folates and Cancer Chemotherapy 263
45. Inability to Increase the Mobilisation of Liver Folates During Folate Deficiency Suggesting that this and Other Organs do not act as a Potential Folate Store for Marrow and Other Rapidly Proliferating Cells 275
46. A High Molecular Weight Nonfunctional Immunoreactive Form of Dihydrofolate Reductase in L1210 Leukaemia Cells 281
47. Further Characterization of the Pterdine Binding Variant of Alphas-Acid Glycoprotein, Accumulated in the Blood of Patients with Malignant Diseases 287
48. Structure-Activity Relationships among 5-Substituted Lipophilic Diaminopyrimidine Antineoplastic Antifolates 293
49. Attempts to Design Inhibitors of Dihydrofolate Reductase Using Interactive Computer Graphics with Real Time Energy Calculations 299
50. Control of Methotrexate Polyglutamate Synthesis in Cultured Rat Hepatoma Cells 305
51. Differential Effects of Methotrexate or Fluorodeoxyuridine upon Mitochondrial and Cellular Nucleotide Pools 311
52. Report on Discussions 317
53. Bioorganic Chemistry and Enzymology
54. Chemical Mechanisms in the Action of Pteridine Coenzymes 321
55. Irreversible Inactivation of Rat Liver Phenylalanine Hydroxylase by Reaction with (6S)-L-Erythro-Tetrahydrobiopterin 345
56. p-Azidophenylalanine: A Potential Photoaffinity Probe for Rat-Liver Phenylalanine Hydroxylase 351
57. Pyrimidine Models for the Cofactor of Phenylalanine Hydroxylase 357
58. Activation of Molecular Oxygen by Tetrahydropterin Monooxygenases 363
59. Mechanistic Studies on Phenylalanine Hydroxylase: Structural Determination of the Tetrahydropterin Intermediates 369
60. Properties of Thymidylate Synthase from Streptococcus Faecium 375
61. Cloning the Gene for Eukaryotic C1-THF Synthase 381
62. Report on Discussions 387
63. Biochemistry and Biology
64. The Enzymatic Synthesis of the Drosopterins: Identification of a Pyrimidodiazepine as an Intermediate 391
65. The Common Precursor of Sepiapterin and Drosopterin in Drosophila: Enzymatic and Chemical Synthesis 397
66. The Common Precursor of Sepiapterin and Drosopterin in Drosophila: Enzymatic and Chemical Synthesis 403
67. The Role of Pteridines in Regulation of Growth 409
68. Evidence for a Folate Bound to Rat Hepatic Uroporphyrinogen III Cosynthase and its Role in the Biosynthesis of Heme 415
69. Report on Discussions 421
70. Presented Papers
71. Aerobic Oxidation of 5,6,7,8-Tetrahydroneopterin 423
72. The Conformations of 7,8 (6H)-Dihydropterin Substrates and the Activity of Dihydropteridine Reductase (E.C.1.6.99.10) 429
73. Dihydrofolate Reductase: The Stereochemistry of Inhibitor Selectivity 435
74. Synthesis of an 8-Deaza Analog of the Intermediate in the Thymidylate Synthetase Reaction (1) 445
75. The Synthesis of Analogs of Pteroylglatamyl-y-Phosphate as Potential Inhibitors of Folylpolyglutamate Synthetase 451
76. Synthesis and Activity of 8,10-Dideazaminopterin 457
77. CNDO/2 Molecular Orbital Calculations on the Antifolate DAMP and Some of its Analogues: Conformational Characteristics 463
78. Fluorescent Analogues of Methotrexate as Probes for Folate Antagonist Molecular Receptors 469
79. Dihydrofolate Reductase Overproduction Identified by Flow Cytometry Using a Fluorescent Methotrexate Analogue 475
80. New Syntheses and Transformations of Some Pteridines and Pteridine 3-Oxides 481
81. Photooxidation of Mercaptopteridines 487
82. Reactivity of 6,7-Dichloro-1, 3-Dimethyllumazine 493
83. Synthesis, Reactivity and Properties of 8-Substituted 2-Thio- and 2,4-Dithiolumazines 499
84. The Activity of Sulfonamide-Substituted Benzylpyrimidines Against Dihydropteroate Synthase, Dihydrofolate Reductase, and Bacterial Cell Cultures 505
85. Structural Studies of Antifolate Drugs 511
86. Isolation and Characterization of a Novel Folate Antagonist 517
87. Synthesis and Biological Properties of the S-8 Analog of 7,8-Dihydropteridinealcohol 523
88. Synthesis of Dihydrobiopterin from Dihydroneopterin Triphosphate in Rat Tissues and Human Blood Corpuscles: Diagnosis of Atypical Phenylketonuria due to Biopterin Deficiency by Assay of an Enzyme Involved in the Synthesis 529
89. Stereospecific Enzyme Mediated Syntheses of Tetrahydrofolate Derivatives 533
90. Immobilization of Dihydrofolate Reductase from Amethopterin Resistant Lactobacillus Casei 539
91. X-Ray Studies of the Binding of Trimethoprim, Methotrexate, Pyrimethamine and Two Trimethoprim Analogues to Bacterial Dihydrofolate Reductase 545
92. A New Spectrophotometry Method for the Assessment of Tight Binding Benzyldiaminopyrimidine Inhibitors of Dihydrofolate Reductase 551
93. Two Interconverting Conformers of a Drug-Receptor Complex: The Lactobacillus Casei Dihydrofolate Reductase-NADP⁺ - Trimethoprim Complex 557
94. Multiple Conformations of the Dihydrofolate Reductase- Folate-NADP⁺ Complex 563
95. The Three-Dimensional Structure of Mouse L1210 Dihydrofolate Reductase 567
96. Isolation and Amino Acid Sequence Studies of Dihydrofolate Reductase from Neisseria Gonorrhoeae 573
97. Purification of 7,8-Dihydropteroate-Synthetase from E. Coli by Affinity- and Hydrophobic Interaction Chromatography 579
98. Isolation and Characterization of an E. Coli Mutant Affected in Dihydrofolate- and Folylpolyglutamate- Synthetase 585
99. Purification and Properties of 5-Formyltetrahydrofolate Cyclodehydrase from Rabbit Liver 591
100. Structural Studies on Formyl-Methenyl-Methylene Tetrahydrofolate Synthetase from Rabbit Liver 597
101. Utilization of Folate Polyglutamate for Growth by Lactobacillus Casei 603
102. Folate and Folate Enzymes as Structural Components of Bacteriophage Particles 609
103. Studies on the Substrate Specificity of Mammalian Folylpolyglutamate Synthetase 615
104. Properties of Corynebacterium Species Dihydrofolate Synthetase-Folylpolyglutamate Synthetase 621
105. Purification and Characterization of Folylpolyglutamate Synthetase from Lactobacillus Casei and Hog Liver 627
106. The Molybdenum Cofactor from Xanthine Oxidase: Quantitative Assay of the Molybdenum Cofactor by Activation of Nitrate Reductase Activity in Extracts of the Nit-1 Mutant of Neurospora crassa 633
107. Structural Studies of Calf Thymus Thymidylate Synthase 639
108. A Comparison of the T-Even Phage Induced and Escherichia Coli Thymidylate Synthases 645
109. Thermophilicity of Dihydrofolate Reductase and Thymidylate Synthetase from a Thermophilic Microorganism 651
110. Chemical Characterization of Two Folate-Binding Proteins from Mitochondria: Dimethylglycine Dehydrogenase and Sarcosine Dehydrogenase 657
111. Allosteric Mung Bean (Vigna radiata) Serine Hydroxylmethyl-Transferase 663
112. Comparative Study of the Eye Colour Mutants of Drosophila Melanogaster: Quantification of the Eye-Pigments and Related Metabolites 669
113. Studies on Sepialumazine, the Characteristic Larval Integument Pigment of the Bombyx Mori Kiuki Mutant 675
114. Macromolecular Regulation of Sepiapterin and Drosopterin Synthesis in the Purple Mutant of Drosophila 681
115. The Hydroxylation of Phenylpropanoids by Euglena gracilis : Role of Pteridines 687
116. Studies with Old Yellow Enzyme, Reconstitution with Lumazine Analogs as Coenzyme 693
117. Biosynthesis of Riboflavin 699
118. Biosynthesis of Riboflavin 705
119. Metabolism and Function of Pterin Compounds in Seed Germination 711
120. Thymidylate Synthetase During Proliferation and Differentiation of Physarum polycephalum 717
121. Influence of Vitamin B₁₂ on Folate Metabolism in Lactobacillus Leichmannii 723
122. High-Affinity Binding of Folate to a Small and Large Molecular Size Protein from Human Milk 729
123. High-Affinity Folate Binding in Leukocytes from Normal Subjects Displays Positive Cooperativity, and the Affinity Depends on the Protein Concentration 735
124. Characteristics of 5-Methyltetrahydrofolate Binding to the Folate-Binding Protein from Cow's Whey 741
125. Interactions of Folate-Dependent Enzymes of DNA Precursor Metabolism in T4 Phage-Infected Bacteria 747
126. The Regulation of Biopterin Biosynthesis in the Rat 753
127. Biosynthesis of Tetrahydrobiopterin in Mammalian Tissues by De Novo and Salvage Pathways 759
128. Perspectives on Tetrahydrobiopterin Biosynthesis in Mammals 765
129. Human Dihydropteridine Reductase (DHPR) Deficiency 771
130. Coordinate Regulation of Guanosine Triphosphate Cyclohydrolase and Tetrahydrobiopterin in Adrenal Medullary Chromaffin Cells 777
131. Regulation of Adrenocortical Guanosine Triphosphate Cyclohydrolase and Tetrahydrobiopterin in Normal and Spontaneously Hypertensive Rats 783
132. Inhibition of Brain Sepiapterin Reductase by a Catecholamine and an Indoleamine 789
133. Mouse Mastocytoma Tryptophan Hydroxylase: Role of Iron and Catalase in the Expression of Enzyme Activity after Activation by Anaerobic Preincubation with Dithiothreitol 795
134. Folic Acid Induced Kindling in Rats: Changes in Brain Amino Acids 801
135. Impaired Pteroylpolyglutamate Synthesis in the Cobalamin-Inactivated Rat 807
136. A Radioimmunoassay for Determination of D-Erythro- Neopterin 815
137. Radioimmunoassay for Neopterin in Body Fluid and Tissues 821
138. A Specific Antiserum Against Tetrahydrobiopterin: Its Preparation and Application to Immunohistochemistry 827
139. Speculation on the Mechanism of Therapeutic Action of Tetrahydrobiopterin in Human Disease 833
140. Correlation of Tetrahydrobiopterin Content and Guanosine Triphosphate Cyclohydrolase Activity in Cells and Tissues 839
141. Unconjugated Pteridines in Human Physiological Fluids. Normal and Pathological Profiles 845
142. Biopterin and Phenylalanine Metabolism During Early Liver Regeneration 851
143. GTP-Cyclohydrolase Activities in Rat Liver 857
144. Phenylalanine Hydroxylase Assay Using Biopterin and Synthetic Pteridine 863
145. Dihydropteridine Reductase Levels in Human Normal and Neoplastic Tissues 869
146. Investigations of Tissue Folates in Normal and Malignant Tissues 875
147. Blood Cell Biopterin as an Indicator of Transplanation- Induced Hemopoiesis and Leukemic Cell Proliferation 879
148. Assessment of Urinary Neopterin in the Early Diagnosis of Human Allograft Rejection 885
149. Behaviour of Neopterin Levels in Patients with Haematological and Gynaecological Neoplasms 891
150. Pteridines in Dictyostelium discoideum and Physarum polycephalum 897
151. Biochemical and Chemotherapy Studies on BW 301U, a Novel Lipophilic 2,4-Diaminopyridopyrimidine Antifolate 903
152. Toxicity of a Series of Antifolate Compounds in a Methotrexate-Resistant Celi Line 909
153. Interaction of Methotrexate Poly(L-Lysine) with Transformed Hepatic Cells in Culture 915
154. A Novel Technique for Producing Folate-Deficient Hepatica Cells 921
155. Methotrexate Metabolism in Acute Lymphoblastic Leukemia 927
156. Altered Methotrexate Sensitivity in Human Leukemic K562 Amino Acid Transport Mutant Cells 933
157. Methotrexate and Methotrexate Polyglutamates in Erythrocytes After High-Dose Methotrexate 941
158. Methotrexate Polyglutamates in Human Fibroblasts: Reversal of Antifolate Cytotoxicity 947
159. Human Cells Resistant to Methotrexate: Cross Resistance and Collateral Sensitivity to the Nonclassical Antifolates Trimetrexate, Metoprine, Homofolic Acid and CB3717 953
160. Homology of Two Forms of Dihydrofolate Reductase in Human Leukaemic and L1210 Cells During Expression of Resistance to Methotrexate 959
161. Adaptation of Folylpolyglutamates to Folate Deprivation in Mouse Hepatoma Cells 965
162. Utilization and Loss of Reduced Folates by Human Fibroblasts in Vitro 971
163. Factors Affecting Folate Polyglutamate Biosynthesis in Rat Liver 977
164. Differential Binding of Folates but not Methotrexate (MTX) by Brush Border (BB) and Basal Lateral (BL) Membranes of Rat Renal Cortex 983
165. Biosynthesis of Folate Derivatives in Ehrlich Ascites Carcinoma Cells Grown in Mice and in some Organs of the Host 989
166. Variability of Thymidylate Synthetase in Ehrlich Carcinoma Cells and its Role in Resistance to 5-Fluorodeoxyuridine 995
167. One-Carbon Metabolism in Human Lymphocytes 1001
168. Possible Mechanisms of Folate Catabolism 1007
169. The Intracellular Folate Pool: Studies of Kinetics and Functional Significance 1013
170. Intestinal Folate Transport. A pH-Dependent, Carrier- Mediated Process 1019
171. Effects of Folate Depletion on Growth and Survival of Human Cell Line K-562 in Culture 1025
172. Alterations in Folate Metabolism of the Rat Induced by Acute Ethanol Administration 1031
173. Participation of Pterins in the Control of Lymphocyte Transformation and Lymphoblast Proliferation 1037
174. The Pterin Component of the Molybdenum Cofactor (Molybdopterin): Relationship to Urothione 1043
175. Report on Presented Papers 1049
176. Author Index 1057
177. Subject Index 1063
178. Backmatter 1072