BETAINE, ETHANOL, AND THE LIVER - A REVIEW

Two of the most important biochemical hepatic pathways in the liver ar e those that synthesize methionine and S-adenosylmethionine (SAM) thro ugh the methylation of homocysteine. This article reviews some recent findings in this laboratory, which demonstrate that ethanol feeding to rats impairs one of these pathways involving the enzyme methionine sy nthetase (MS), but by way of compensation increases the activity of th e enzyme betaine:homocysteine methyl transferase (BHMT), which catalyz es the second pathway in methionine and SAM biosynthesis. It has been shown that despite the inhibition of MS, the enhanced BHMT pathway uti lizes hepatic betaine pools to maintain levels of SAM. Subsequent to t he above findings, it has been shown that minimal supplemental dietary betaine at the 0.5% level generates SAM twofold in control animals an d fivefold in ethanol-fed rats. Concomitant with the betaine-generated SAM ethanol-induced hepatic fatty infiltration was ameliorated. In vi ew of the fact that SAM has already been used successfully in the trea tment of human maladies, including liver dysfunction, betaine, shown t o protect against the early stages of alcoholic liver injury as well a s being a SAM generator, may become a promising therapeutic agent and a possible alternative to expensive SAM in the treatment of liver dise ase and other human maladies.