Ebook: Chemistry and Biology of Pteridines and Folates: Proceedings of the 12th International Symposium on Pteridines and Folates, National Institutes of Health, Bethesda, Maryland, June 17–22, 2001

Pteridine and folate research has long been recognized as important for many biological processes, such as amino acid metabolism, nucleic acid synthesis, neurotransmitter synthesis, cancer, cardiovascular function, and growth and development of essentially all living organisms. Defects in synthesis, metabolism and/or nutritional availability of these compounds have been implicated as major causes of common disease processes, e.g. cancer, inflammatory disorders, cardiovascular disorders, neurological diseases, autoimmune processes, and birth defects.
Since pteridine and folate biology uses concepts and experimental techniques drawn from all of these disciplines, the breadth of this volume is its great strength, bringing together researchers from a wide variety of fields including biochemistry, chemistry, physics, biophysics, genetics, microbiology, cell and molecular biology, virology, immunology, cancer, neurobiology and medicine. This volume should be a valuable and unique reference work for scientists with interests in these areas as well as those seeking up to date information.

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Pteridine and folate research has long been recognized as important for many biological processes, such as amino acid metabolism, nucleic acid synthesis, neurotransmitter synthesis, cancer, cardiovascular function, and growth and development of essentially all living organisms. Defects in synthesis, metabolism and/or nutritional availability of these compounds have been implicated as major causes of common disease processes, e.g. cancer, inflammatory disorders, cardiovascular disorders, neurological diseases, autoimmune processes, and birth defects.
Since pteridine and folate biology uses concepts and experimental techniques drawn from all of these disciplines, the breadth of this volume is its great strength, bringing together researchers from a wide variety of fields including biochemistry, chemistry, physics, biophysics, genetics, microbiology, cell and molecular biology, virology, immunology, cancer, neurobiology and medicine. This volume should be a valuable and unique reference work for scientists with interests in these areas as well as those seeking up to date information.

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Pteridine and folate research has long been recognized as important for many biological processes, such as amino acid metabolism, nucleic acid synthesis, neurotransmitter synthesis, cancer, cardiovascular function, and growth and development of essentially all living organisms. Defects in synthesis, metabolism and/or nutritional availability of these compounds have been implicated as major causes of common disease processes, e.g. cancer, inflammatory disorders, cardiovascular disorders, neurological diseases, autoimmune processes, and birth defects.
Since pteridine and folate biology uses concepts and experimental techniques drawn from all of these disciplines, the breadth of this volume is its great strength, bringing together researchers from a wide variety of fields including biochemistry, chemistry, physics, biophysics, genetics, microbiology, cell and molecular biology, virology, immunology, cancer, neurobiology and medicine. This volume should be a valuable and unique reference work for scientists with interests in these areas as well as those seeking up to date information.
Content:
Front Matter....Pages i-xxiii
Making Methionine: A Love Affair with Folate....Pages 1-8
Structure Elucidations of Dimeric Pteridines....Pages 9-17
A Selective Procedure for 6-Subsituted Pterin Derivatives: Synthesis and Substitution of Pterin 6-Triflate....Pages 19-23
Solution and Solid Phase Synthesis of Pteridines, Purines and Related Compounds....Pages 25-29
Synthesis of Pteridines With C-2 And C-6 Functional Group Diversity....Pages 31-35
Stereospecific Synthesis of 2-Desamino-Tetrahydropterins as Probes of Hydroxylase Cofactor Recognition....Pages 37-41
New Pyranopterin Chemistry Related to Molybdenum and Tungsten Enzymes....Pages 43-47
Application of FDCD Spectroscopy for Determination of Chiralities of Biologically Important Pteridines....Pages 49-53
Regulation of Tyrosine Hydroxylase by S-Glutatiolation: Relevance to Conditions Associated with Dopamine Neuronal Damage....Pages 55-59
The Conformation of Tetrahydro-Biopterin Free and Bound to Aromatic Amino Acid Hydroxylases and NOS....Pages 61-65
Regulatory Properties of the Tetrahydropterin Cofactor in the Reaction Catalysed by Human Tyrosine Hydroxylase Isoforms 1–4....Pages 67-72
Structure and Regulation of Phenylalanine Hydroxylase, and Implications for Related Enzymes....Pages 73-77
Interaction of Phosphorylated Tyrosine Hydroxylase with 14-3-3 Proteins: Effects on Phosphorylation Kinetics....Pages 79-84
Mechanistic Studies of Tryptophan Hydroxylase....Pages 85-89
Role of PHE313/TRP326 in Determining Substrate Specificity in Tryptophan and Phenylalanine Hydroxylases....Pages 91-95
Possible Contributions of Labile Asparagine Residues to Differences in Regulatory Properties of Human and Rat Phenylalanine Hydroxylase....Pages 97-102
3-(2-Thienyl)-L-Alanine as a Competitive Substrate Analogue and Activator of Human Phenylalanine Hydroxylase....Pages 103-107
The N-Terminus of Human Tyrosine Hydroxylase is Responsible for its Association with Phospholipid Bilayers....Pages 109-113
Mechanisms of Tyrosine Hydroxylase Activation by Stress Activated Protein Kinases....Pages 115-119
Substrate Specificities of Phenylalanine and Tyrosine Hydroxylase: Role of Aspartate 425 of Tyrosine Hydroxylase....Pages 121-126
Mutation of W457 Alters N-Hydroxy-L-Arginine Oxidation by Inducible no Synthase: A Single Turnover Study....Pages 127-132
Estradiol Modulates GTP Cyclohydrolase I Gene Expression in Brain Catecholaminergic Systems....Pages 133-138
PKC-mediated Regulation of GTP Cyclohydrolase I in Mast Cells and Renal Mesangial Cells....Pages 139-144
Regulation of GTP Cyclohydrolase I by Estrogen....Pages 145-149
Sexually Dimorphic GTP Cyclohydrolase I Gene Expression is Independent of Sex Hormones....Pages 151-155
Studies on the Reaction Mechanism of GTP Cyclohydrolase I....Pages 157-161
Site-Directed Mutagenesis of Residues in the Active Site of Sepiapterin Reductase....Pages 163-167
Determination of Residues of Sepiapterin Reductase Phosphorylated by Ca2+/Calmodulin-Dependent Protein Kinase II....Pages 169-173
The Interaction of GTP Cyclohydrolase I and GTP Cyclohydrolase Feedback Regulatory Protein Can be Detected using the Yeast Two-Hybrid System....Pages 175-179
Co-Induction of Tetrahydrobiopterin and Catecholamine Syntheses in V-l-OVerexpressing PC12D Cells....Pages 181-185
Sepiapterin Administration Raises Tissue BH4 Levels More Efficiently Than BH4 Supplement in Normal Mice....Pages 187-191
Cells Take up BH4, Oxidize It and the Oxidized Biopterin is Preferentially Released....Pages 193-197
The Pteridine Pathway in the Zebrafish, Danio Rerio: Development in Neural Crest-Derived Cells and Its Control by GTP Cyclohydrolase I....Pages 199-204
Tetrahydrobiopterin, Nitric Oxide Synthesis and cGMP Concentrations in Mutants of Physarum Polycephalum with Altered Sporulation Behavior....Pages 205-210
Tetrahydrobiopterin and Vascular Endothelial Function....Pages 211-215
L-Ascorbic Acid Increases Intracellular Tetrahydrobiopterin Via A Chemical Stabilization and Potentiates Nitric Oxide Synthesis in Endothelial Cells....Pages 217-222
The Redox Status of Bound Pterin Cofactor Determines Whether eNOS Produces NO or Superoxide Anion: [3H]-BH4 Binding Studies Provide Insights into Vascular Pathophysiology....Pages 223-228
Sepiapterin Reductase Deficiency: Molecular Analysis in a New Case Presenting with Neurotransmitter Deficiency without Hyperphenylalaninemia....Pages 229-234
Molecular Basis of DOPA-Responsive Dystonia....Pages 235-239
Human Nigrostriatal Dopamine Neurons Express Low Levels of GTP Cyclohydrolase I mRNA....Pages 241-246
Immunosuppressive Effects of the 4-Amino Analogue of Tetrahydrobiopterin....Pages 247-251
Tetrahydrobiopterin Responsive Hyperphenylalaninemia without Biopterin Deficiency....Pages 253-257
The Fate of Intravenously Administered Tetrahydrobiopterin and Its Implications for Heterologous Gene Therapy of Phenylketonuria....Pages 259-263
Influence of Hydrogen Peroxide (H2O2) on Pterin Homeostasis in the Depigmentation Disorder Vitiligo....Pages 265-270
Catechol-O-Methyltransferase Inhibition in the Treatment of Tetrahydrobiopterin Deficiency....Pages 271-276
Changes in Dihydropteridine Reductase (DHPR) Activity of the Occupationally Lead Exposed Workers....Pages 277-284
Clinical Utility of Pteridine Measurement in Cerebrospinal Fluid....Pages 285-289
Effect of Ascorbic Acid in Measurement of Serum Pteridine Concentration....Pages 291-295
The Effect of Tetrahydrobiopterin (BH4) on Sperm Motility....Pages 297-300
Tetrahydrobiopterin Deficiency in Diabetic Rats....Pages 301-304
The Effect of Tetrahydrobiopterin (BH4) on Diabetic Nephropathy in Streptozotocin (STZ) Induced Diabetic Rats....Pages 305-308
Determination of Sepiapterin and Sepiapterin Reductase in Human Skin....Pages 309-317
Neopterin, an Immunodiagnostic and Oxidative Stress Indicator....Pages 319-328
Role of Neopterin in Immune Monitoring in Transplant Medicine....Pages 329-334
Neopterin and 7,8-Dihydroneopterin-Induced Signal Transduction Cascades in Cell Lines....Pages 335-339
Determination of Neopterin Levels in Gingival Crevicular Fluid (GCF)....Pages 341-344
Neopterin and Biopterin Levels in Pregnancy....Pages 345-348
Tetrahydrobiopterin (BH4)-Mediated Neuronal Death Following Intrastriatal Kainic Acid: Implications for Parkinson’s Disease....Pages 349-353
Inhibition of Oxidative Stress during Developmental Cell Death: Cellular and Behavioral Effects....Pages 355-358
The Role of Tetrahydrobiopterin (BH4) in Trophic Factor Withdrawal-Induced Apoptosis in PC12 Cells....Pages 359-363
Apoptotic Death of PC12 cells Induced by Ischemia-Like Conditions is Mediated by Tetrahydrobiopterin (BH4) Metabolism....Pages 365-369
New Approaches Towards Inhibitors of Folate-Dependent Enzymes: Rapid Synthesis of 5-Deazapterins From Uracil Derivatives....Pages 371-375
Solid and Solution Phase Strategies for the Synthesis of Potential Inhibitors of Folate Biosynthesis....Pages 377-381
Progress Towards the Synthesis of Pyrimidodiazepine-Based Folates as Potential Inhibitors of Glycinamide Ribonucleotide Formyltransferase....Pages 383-386
Role of P53 Status on Sensitivity to Thymidylate Synthase Inhibitors and Induction of Apoptosis....Pages 387-391
Synthesis of N-[4-[(2-Amino-6-Methyl-3,4-Dihydro-4-Oxo-7H-Pyrrolo[2,3-d]-Pyrimidin-5-Yl)Methyl]Benzoyl]-L-Glutamic Acid as an Antifolate....Pages 393-397
Effect of Bridge Truncation of Classical 2,4-Diamino-5-Substituted Furo [2,3-d] Pyrimidine and 2-Amino-4-Oxo-6-Substituted Pyrrolo [2,3-d] Pyrimidine on Antifolate Activity....Pages 399-403
Selection of Methotrexate-Resistant Lactobacillus Casei in the Presence of Folate or 5-Formyl-Tetrahydrofolate Affects the Resistance Mechanism....Pages 405-408
Molecular Mechanisms of Resistance to Antimalarial Antifolate Drug Pyrimethamine-Sulfadoxine....Pages 409-413
5-Fluorouracil Induction of Fas and Apoptosis in Colon Cancer Patients: Relation of Clinical Outcome with Thymidylate Synthase, Mcl-1 and Rb....Pages 415-420
Synthesis of 2- or 4-Seleno Analogues of dUMP and FdUMP, and the Corresponding Nucleosides. Interactions with Mammalian Tumour Thymidylate Synthase of the Selenonucleotides and Inhibition of Tumor Cell Growth by the Selenonucleosides....Pages 421-425
Induction of Resistance to the Multi-Targeted Antifolate MTA (LY231514) in Widr Human Colon Cancer Cells....Pages 427-431
Mutational Studies of an Essential Glutamate Residue in Escherichia Coli Folylpolyglutamate Synthetase with a Role in ATP Binding....Pages 433-437
Rapid Purification of the T-Protein of the Glycine Cleavage System from Rabbit Liver....Pages 439-443
Effects of Cellular Glycine on Cell Proliferation....Pages 445-450
Microarray Analysis of Genes Induced by Methionine Starvation and Growth on Different Sulfur Sources in Yeast....Pages 451-456
Gene Structure and Expression of Trichinella Spiralis Thymidylate Synthase....Pages 457-460
Lack of Mutation of L1210 Thymidylate Synthase with Altered Sensitivity to FdUMP Inhibition....Pages 461-466
Enzymes of Thymidylate Biosynthesis in Trichinella Pseudospiralis Muscle Larvae and Caenorhabditis Elegans Dauer Larvae....Pages 467-471
Thymidylate Synthase Heterogeneity Assessed by Monoclonal Antibodies....Pages 473-477
Structure-Based Modeling of Reversed N9-C10 Bridge Antifols with Human, PC and TG DHFR....Pages 479-483
Biochemical Studies of Human Methionine Synthase Reductase....Pages 485-489
Model Studies for the B12 Dependent Methyltransferases....Pages 491-494
Betaine-Homocysteine S-Methyl-Transferase (BHMT) Transcription is Inhibited by S-Adenosylmethionine (AdoMet)....Pages 495-500
Can Elevated Plasma Homocysteine Levels Result in the Inhibition of Intracellular Methyltransferases?....Pages 501-505
The Neuropathy of Disturbed Brain Methylation Reactions....Pages 507-511
Dopamine-Stimulated Solid-State Signaling: A Novel Role for Single-Carbon Folates in Human Attention....Pages 513-517
Is Moderate Hyperhomocysteinemia Due to Folic Acid Depletion Rather than Insufficient Dietary Intake?....Pages 519-523
C677T MTHFR Genotype is a Risk Factor for Thromboembolism: Comparison of T Allele Frequency and Homocysteine Level Between Female Thromboembolic and Non-Thromboembolic Vascular Patients, NTD Mothers and Matched NTD Controls....Pages 525-529
Molecular Bases of Hyper-Homocysteinemia due to Inborn Errors of Folate and Cobalamin Metabolism....Pages 531-535
Vitamin B6 (PLP) and Neural Tube Defects: Is There an Association?....Pages 537-542
Erythrocyte Folate Levels in Operating Room Personnel....Pages 543-547
A Human Ileostomy Model to Determine Folate Bioavailability from Food....Pages 549-556
12 Channel Coulometric Electrochemical Detection for the Identification of Polyglutamate Homology Amongst Cellular Folates....Pages 557-562
Gastro-Intestinal pH Modulates Facile Interconvertion of Native Formylfolates During Absorption....Pages 563-568
Control of Folate Production in Lactic Acid Bacteria by Using Metabolic Engineering....Pages 569-574
Evidence for a Cryptic Gene that Enables E. Coli to Specifically Transport Folate Analogs....Pages 575-579
Folate Transport Abnormalities and Congenital Defects....Pages 581-585
Role of Multidrug Resistance Proteins (MRP) in Resistance to Antifolates and Folate Homeostasis....Pages 587-591
Kinetics of Reduced Folate Carrier-and Membrane-Associated Folate Receptor-Mediated Transport of Antifolates....Pages 593-599
Cell Biology and Regulation of the Intestinal Folate Absorption Process....Pages 601-607
Back Matter....Pages 609-613
....Pages 615-618