Protein and amino acid metabolismAmino acids and the regulation of methyl balance in humansBrosnan, John T; da Silva, Robin; Brosnan, Margaret EAuthor Information Department of Biochemistry, Memorial University of Newfoundland, St John's, Newfoundland, Canada Correspondence to Dr J.T. Brosnan, DPhil, DSc, Department of Biochemistry, Memorial University of Newfoundland, St John's, NL A1B 3X9, Canada Tel: +1 709 737 8540; fax: +1 709 737 2422; e-mail: [email protected] Sponsorship: Research by the authors cited in this paper has been supported by the Canadian Institutes for Health Research. Current Opinion in Clinical Nutrition and Metabolic Care: January 2007 - Volume 10 - Issue 1 - p 52-57 doi: 10.1097/MCO.0b013e3280110171 Buy Metrics Abstract Purpose of review To outline recent advances in our understanding of the metabolic basis for the maintenance of cellular S-adenosylmethionine levels and, thus, for facilitating the many crucial methylation reactions in the body. Amino acids are intimately involved in these processes. Recent findings The application of stable-isotope methodology has permitted accurate estimation of the total transmethylation flux in humans. Chemical balance studies have identified the quantitatively major transmethylation reactions. New evidence points to a key role for deranged S-adenosylmethionine metabolism in the pathogenesis of liver disease. Mutations in key enzymes point to the importance of methyl metabolism in closure of the neural tube, synthesis of creatine and metabolic clearance of methionine. Dietary interventions designed to affect S-adenosylmethionine availability to pregnant mice have been shown to modulate the epigenetic DNA methylation of specific genes. Summary These findings are of relevance to the pathogenesis of neural tube defects as well as the interaction between a genetic polymorphism and nutritional status. They also address the issue of methyl group availability and epigenetic regulation. Finally, they are also relevant to the etiology of cirrhosis and steatohepatitis. © 2007 Lippincott Williams & Wilkins, Inc.