Homocysteine In Health And Disease

This is an unusually comprehensive 2001 account of the broad range of medical implications of homocysteine.

This book comprehensively reviews the association of homocysteine metabolism with the etiology of various human disorders. The well-defined chapters embedded the central and peripheral effects of homocysteine metabolism intricately related with cardiovascular, neurodegenerative, metabolic, and autoimmune disorders. Further, it discusses the mechanisms of perturbance of cellular proteostasis by elevated homocysteine levels and provides a comprehensive account of pathophysiological consequences and clinical implications of homocysteine-containing proteins. The book also reviews association of genetic variants of homocysteine metabolic genes with type 2 diabetes mellitus and obesity. It also describes the molecular mechanism of hyperhomocysteinemia in the negative/feedback regulation of neural stem cell proliferation and alterations in DNA methylation. Taken together, it summarizes the mechanisms of hyper homocysteinemia-induced endothelial dysfunction and physiological functions of hydrogen sulfide as the protective agent.

Excess of homocysteine, a product of the metabolism of the essential amino acid methionine, is associated with poor health, is linked to heart and brain diseases in general human populations, and accelerates mortality in heart disease patients. Neurological and cardiovascular abnormalities occur in patients with severe genetic hyperhomocysteinemia and lead to premature death due to vascular complications. Although it is considered a non-protein amino acid, studies over the past dozen years have discovered mechanisms by which homocysteine becomes a component of proteins. Homocysteine-containing proteins lose their normal biological function and become auto-immunogenic and pro-thrombotic. In this book, the author, a pioneer and a leading contributor to the field, describes up-to date studies of the biological chemistry of homocysteine-containing proteins, as well as pathological consequences and clinical implications of their formation. This is a comprehensive account of the broad range of basic science and medical implications of homocysteine-containing proteins for health and disease. ​

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As a result of over 17,500 published investigations, the obscure sulphur amino acid homocysteine was elevated to the status of the cholesterol of the 21st century because of its prominent involvement in human vascular disease. Extensive human studies identified the elevation of plasma homocysteine as a potent, independent risk factor for vascular disease, including coronary heart disease, cerebrovascular disease, and peripheral vascular disease. Many other important human diseases were subsequently found to be affected by homocysteine, as described by the authors of several chapters in the present book. These diseases, many of which are correlated with ageing, include neurodegenerative diseases and dementia, epilepsy, uremia, osteoporotic fractures, anaemia of renal failure, infection by HIV+, glaucoma, macular degeneration, bariatric surgery for obesity, celiac disease and psoriasis.

This is an important and timely volume. The history of research in homocysteine metabolism can be divided into three periods. The first phase was the exploration of the individual reactions and metabolites that characterize the transmethylation and transsulfuration sequences. The former originated with his description of the biosynthesis of methylpyridine and culminated in the work of Cantoni and Axelrod. Similarly the finding that insulin contained cystine was a potent catalyst for the metabolic and nutritional studies of Rose and du Vigneaud. The description and the definition of homocystinuria, a rare inherited meta bolic disorder, marked the beginning of the second historical period. Where previously there had been few laboratories located largely in the United States soon there were numerous research groups representing many nationalities. The more intense focus led to major advances, both in the laboratory and in the clinics. Studies of afflicted individuals, when combined with investigations in experimental animals, provided the basis for a concept of methionine metabo lism that encompassed both transmethylation and transsulfuration. The central role of homocysteine was apparent.

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