Methionine synthase. a possible prime site of the ethanolic lesion in liver

Among the most important pathways for liver integrity in the body are the two that synthesize methionine and S-adenosylmethionine (SAM) through methylation of homocysteine. Results of studies in this laboratory have demonstrated ethanolic inhibition of one of these pathways catalyzed by methionine synthetase. It has been shown elsewhere that alcohol per se does not inhibit the enzyme, but that the metabolite of ethanol, acetaldehyde, is responsible through the formation of an inhibiting covalent adduct. Because hepatic SAM has been shown to be essential in the transport of fat from the liver, avoiding steatosis and further liver damage, it is entirely feasible that this repression of methionine synthase is an important site of the injurious action of alcohol metabolism in the liver. This loss of activity is particularly important in human beings who cannot produce methionine and SAM by means of the alternate pathway mediated by betaine:homocysteine:transmethylase, because of the lack of production of the betaine substrate for this enzyme.