Amino acids and the regulation of methyl balance in humans

Abstract

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. 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. 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.