Two of the most important biochemical hepatic pathways in the liver are those that synthesize
methionine and
S-adenosylmethionine (SAM) through 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 synthetase (MS), but by way of compensation increases the activity of the
enzyme betaine:
homocysteine methyl
transferase (BHMT), which catalyzes the second pathway in
methionine and SAM biosynthesis. It has been shown that despite the inhibition of MS, the enhanced BHMT pathway utilizes hepatic
betaine pools to maintain levels of SAM. Subsequent to the above findings, it has been shown that minimal supplemental dietary
betaine at the 0.5% level generates SAM twofold in control animals and fivefold in
ethanol-fed rats. Concomitant with the
betaine-generated SAM,
ethanol-induced hepatic fatty infiltration was ameliorated. In view of the fact that SAM has already been used successfully in the treatment of human maladies, including
liver dysfunction,
betaine, shown to protect against the early stages of alcoholic liver injury as well as being a SAM generator, may become a promising therapeutic agent and a possible alternative to expensive SAM in the treatment of
liver disease and other human maladies.