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Hyperhomocysteinemia and Risk of Atherosclerosis, Cardiovascular Disease and Cancer: A Concise Update

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Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia
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Abstract

Homocysteine is a sulfur-containing amino acid obtained from the metabolism of methionine. Dietary methionine is converted to S-adenosylmethionine and is demethylated to S-adenosylhomocysteine and homocysteine. Under conditions of protein deficient diet, intracellularly homocysteine is metabolized by one of two pathways: re-methylation and trans-sulfuration where vitamin B12 and folic acid participate as cofactors respectively. In the folate cycle, the enzyme methionine synthase and vitamin B12 as well as the enzyme 5,10-methylenetetrahydrofolate reductase are required. Folate enters the re-methylation cycle and is converted to 5-methyltetrahydrofolate, an important methyl donor in the conversion of homocysteine to methionine. Remethylation reactions also occur in the liver in which the enzyme betaine homocysteine methyltransferase, transfers a methyl group to homocysteine via the demethylation of betaine to dimethylglycine [1]. Therefore, disruption of S-adenosylmethionine -dependent transmethylation reactions leads to high concentrations of homocysteine in the blood and has been associated with deleterious effects. The normal level of homocysteine ranges between 5–15 μM, however in diseased conditions it can range from 50 μM in mild cases to 500 μM in severe cases [2]. The etiology of cancer is multifactorial. Studies have established a close association between cancer and hyperhomocystinemia [3]. Genetic & environmental factors play an important role in its pathogenesis. High levels of homocysteine are found in epigenetic regulation of DNA silencing and posttranslational modification of histones [3]. Specifically, the carcinogenic potential of hyper homocysteinemia is dependent on the detoxification pathways in homocysteine metabolism, venous thromboembolism, deficiency of folate and/or polymorphisms. In this chapter, the role of homocysteine on atherosclerosis, cardiovascular disease and cancer is discussed.

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Taranikanti, V. (2021). Hyperhomocysteinemia and Risk of Atherosclerosis, Cardiovascular Disease and Cancer: A Concise Update. In: Waly, M.I. (eds) Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia. Springer, Cham. https://doi.org/10.1007/978-3-030-57839-8_12

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