Effect of nicotinamide on methionine metabolism in rat liver.

To test the response to increased utilization of methyl groups, we administered large dosages of nicotinamide to rats fed an adequate diet that contained limited amounts of methionine and choline. During the 4 d after the injection, we observed several significant effects on the hepatic concentrations of the enzymes and metabolites of methionine metabolism. Methionine and S-adenosylmethionine remained at control levels; the concentrations of S-adenosylhomocysteine exceeded the control values from 4 to 16 h; and the levels of serine and betaine were lower after 16 h. Treatment with nicotinamide resulted in higher hepatic levels of methionine adenosyltransferase (after 4 h) and cystathionine synthase (after 16 h). These data indicate that increases in both homocysteine methylation and S-adenosylmethionine synthesis may be components of the response to excessive methyl group consumption. An increased synthesis of cystathionine would provide for the removal of S-adenosylhomocysteine (and homocysteine) derived from the adenosylmethionine-dependent methylation of nicotinamide.