Arsenic Methylation and the S-Adenosylmethionine-Mediated Transmethylation/Transsulfuration Pathway

摘要

Studies of arsenic and its methylated metabolites in the urine of humans demonstrate that there is considerable variation in the methylation of arsenic. One of the biochemical pathways that may influence the degree of methylation is the S-adenosylmethionine transmethylation/transsulfuration pathway. This pathway is the site of a number of known genetic defects influencing the fate of methionine and various intermediary metabolites. Although the homozygous defects are fairly rare, little is known about the distribution of heterozygosity in different populations and its impact on transmethylation reactions. Other factors that influence the pathway include the presence of competing substrates for methyl groups such as norepinephrine, cobalamin and phosphatidyl ethanolamine. The fate of intermediary metabolites such as homocysteine, and the demand for, and dietary adequacy of the sulfur-containing amino acids (methionine and cysteine) are other determinants that influence pathway function. Insufficient levels of the B vitamins (folk acid, cobalamin and vitamin B-6) can place additional stress on methylation efficacy. Each of these variables is considered from the perspective of its ability to affect the methylation of arsenic either directly or indirectly.