Hepatic metabolism of sulfur amino acids in db/db mice.

To determine the effect of type-2 diabetes and obesity on the hepatic metabolism of sulfur amino acids, hepatic sulfur amino acid metabolism was determined in db/db mice. Hepatic methionine was markedly decreased in db/db mice, although the hepatic activity of betaine homocysteine methyltransferase was increased. The decrease in hepatic methionine was reflected by decreased sulfur-containing methionine metabolites, including S-adenosylmethionine, homocysteine, cysteine, and hypotaurine in liver and plasma. In contrast, S-adenosylhomocysteine, putrescine, and spermidine were increased in db/db mice. The hepatic level and activity of methionine adenosyltransferase I/III, an S-adenosylmethionine synthesizing enzyme, were significantly increased. These results suggest that increased polyamine synthesis, in conjunction with decreased hepatic methionine levels, is partly responsible for the reduction in hepatic S-adenosylmethionine. Decreased homocysteine in liver and plasma may be attributable to the decrease in hepatic methionine and upregulation of hepatic betaine homocysteine methyltransferase. Glutathione in liver and plasma did not change despite decreased γ-glutamylcysteine ligase activity. The decreased hepatic hypotaurine may be attributable to the downregulation of cysteine dioxygenase. The major finding of this study is that db/db mice exhibited decreases in hepatic methionine and its sulfurcontaining metabolites.