In 1962, 30 years after the discovery by du Vigneaud have pathologic consequences. One potentially sig of a new sulfur amino acid, homocysteine; Carson and nificant health outcome of such mild to moderate Neil reported two siblings with mental retardation in hyperhomocysteinemia is an increased risk of occlu northern Ireland with elevated urinary homocystine. sive vascular disease. Homocysteine concentrations in Nearly simultaneously, Gerritsen and Waisman patients with vascular disease were, on average, 31 % greater than in normal controls. Prospective assess identified increased homocystine in the urine of a mentally retarded infant in Wisconsin. Within two ment of vascular disease risk among men with higher years, Harvey Mudd, James Finkelstein, and their homocysteine concentrations indicated that plasma coworkers at the National Institutes of health (USA) homocysteine at only 12% above the upper limit of that the enzyme cystathionine ~ normal levels was associated with a 3. 4-fold increase had reported synthase was lacking in a liver biopsy specimen from in risk of acute myocardial infarction. Studies from another patient with homocystinuria. This was the original Framingham Heart Study cohort (USA) the first indication of a vitamin relationship to have shown strong, positive correlation between homocystinuria, because that enzyme has as its co plasma homocysteine concentration and degree of factor vitamin B6 (pyridoxal phosphate). Thereafter, carotid stenosis.

Klappentext

This volume is the first comprehensive treatise on homocysteine to treat the topic from the basic biochemical, metabolic, genetic, and dietary determinants to disease relationships, including concepts of pathogenesis. In addition, the public health implications of these associations are described. To date, evidence strongly supports the hypotheses that Hyperhomocysteinemia is a strong independent determinant of vascular disease and Many cases of hyperhomocysteinemia are amenable to homocysteine-lowering treatment with B-vitamins.£/LIST£ The strength of this evidence is prompting discussion of large-scale homocysteine-lowering interventions. Against this background of growing recognition of the importance of homocysteine as a factor in coronary artery disease, cerebrovascular disease, stroke, and peripheral vascular disease, the editors conceived of a state-of-the-art monograph on homocysteine and its relationships to disease. The contributors would be those scientists who, in fact, had written the history of this field of study over the past third of a century. The editors invited the leading investigators in the world to contribute chapters in their own areas of expertise to this monograph and to deliver those papers at the first International Meeting on Homocysteine in Ireland, which has emerged as an important study center and where the first cases of homocystinuria were reported more than three decades ago.

Inhalt
I. Biochemistry And Genetic Studies.- 1. The Regulation of Homocysteine Metabolism.- 2. Methionine Kinetics and Balance.- 3. On the Formation and Fate of Total Plasma Homocysteine.- 4. Methylenetetrahydrofolate Reductase: Comparison of the Enzyme from Mammalian and Bacterial Sources.- 5. Genetics of Mammalian 5,10-methylenetetrahydrofolate Reductase.- 6. Thermolabile Methylenetetrahydrofolate Reductase.- 7. The Long-term Outcome in Homocystinuria.- 8. Characterization of the Human and Porcine Methionine Synthases and their Redox Partners.- 9. Inherited Disorders of Folate and Cobalamin.- 10. Molecular Genetics of Cystathionine ?-Synthase in Homocystinuria and Vascular Disease.- 11. Cystathionine ?-synthase Deficiency: Metabolic Aspects.- II. Vitamins, Pathology, And Drug Therapy.- 12. Homocysteine and Other Metabolites in the Diagnosis and Follow-up of Cobalamin and Folate Deficencies.- 13. Vitamin Status and Hyperhomocysteinemia in a Healthy Population.- 14. Association Between Plasma Homocysteine, Vitamin Status, and Extracranial Carotid-Artery Stenosis in the Framingham Study Population.- 15. Treatment of Mild Hyperhomocysteinemia.- 16. Folate, Vitamin B12, and Neuropsychiatric Disorders.- 17. Vitamins, Homocysteine, and Neural-Tube Defects.- 18. The Etiology of Neural Tube Defects.- 19. Plasma Homocysteine in Renal Failure, Diabetes Mellitus, and Alcoholism.- 20. Homocysteine and Drug Therapy.- III. Homocysteine, Cancer, And Cardiovascular Disease.- 21. Is Methionine Useful for the Prevention of Hyperhomocysteinemia-Associated Cardiovascular Disease?.- 22. Synthesis of Homocysteine Thiolactone in Normal and Malignant Cells.- 23. Folate Status: Modulation of Colorectal Carcinogenesis.- 24. The Hordaland Homocysteine Study: Lifestyle and Total Plasma Homocysteine inWestern Norway.- 25. Blood Homocysteine Levels in the National Health and Nutrition Examination Survey (NHANES III) in the United States: Preliminary Findings by Age and Sex.- 26. Heritability of Plasma Homocysteine Concentration.- 27. Plasma Homocysteine and Coronary Artery Disease.- 28. Homocysteine and Cerebral and Peripheral Vascular Disease.- 29. Plasma Homocysteine and its Relationship to Cardiovascular Risk Factors in a Japanese Population.- 30. Biological Chemistry of Thiols in the Vasculature and in Vascular-Related Disease.- IV. Intervention Studies and Concepts for the Future.- 31. Homocysteine and Vascular Disease: The European Concerted Action Project.- 32. Prospective Studies of Homocysteine and Vascular Disaese.- 33. A Meta-Analysis of Plasma Homocysteine as a Risk Factor for Arteriosclerotic Vascular Disease and the Potential Preventive Role of Folic Acid.- 34. Pathology of Homocystinuria.- 35. Lipoprotein(a), Homocysteine, and Atherogenesis.- 36. Endothelial- and Leukocyte-Mediated Mechanisms in Homocysteine-Associated Occlusive Vascular Disease.