Effect of acute ethanol administration on S-amino acid metabolism: increased utilization of cysteine for synthesis of taurine rather than glutathione.

Alterations in the hepatic metabolism of S-amino acids were examined in male rats injected with a single dose of ethanol (3 g/kg, i.p.). The hepatic concentrations of methionine and S-adenosylhomocysteine (SAH) were increased, but S-adenosylmethionine (SAM), cysteine, and glutathione (GSH) decreased rapidly following ethanol administration. The activities of methionine adenosyltransferase (MAT), cystathionine beta-synthase (CbetaS) and cystathionine gamma-lyase (CgammaL) were all inhibited. Gamma-glutamylcysteine synthetase (GCS) activity was increased from t = 8 hr, but hepatic glutathione (GSH) level did not return to control for 48 hr. Both hepatic hypotaurine and taurine levels were increased immediately, which were reduced to below control from t = 18 hr. Changes in the serum concentration of taurine were consistent with results observed in the liver. Cysteine dioxygenase (CDO) activity was increased rapidly, but declined from t = 24 hr. The results indicate that an acute dose of ethanol induces significant alterations in the metabolism of S-amino acids in the liver. Ethanol depresses the cysteine availability for GSH synthesis not only by inhibiting the transsulfuration reactions but also by enhancing its irreversible catabolism to taurine via hypotaurine. The physiological significance of this finding is discussed.

Effect of acute betaine administration on hepatic metabolism of S-amino acids in rats and mice.

Alterations of hepatic glutathione level by betaine were observed previously. In this study effects of betaine administration (1000 mg/kg, i.p.) on S-amino acid metabolism in rats and mice were investigated. Hepatic glutathione level decreased rapidly followed by marked elevation in 24 hr. Concentrations of S-adenosylmethionine, S-adenosylhomocysteine, and methionine were increased whereas cystathionine decreased significantly, suggesting that homocysteine generated in the methionine cycle is preferentially remethylated to methionine rather than being utilized for synthesis of cysteine. Hepatic cysteine concentration declined immediately, but plasma cysteine increased. Effect of betaine on hepatic cysteine uptake was estimated from the difference in cysteine concentration in major blood vessels connected to liver. Cysteine concentration either in the portal vein or abdominal aorta was not altered, however, a significant increase was noted in the hepatic vein, indicating that hepatic uptake of cysteine was decreased by betaine treatment. Activities of glutamate cysteine ligase, cystathionine beta-synthase, and cystathionine gamma-lyase were elevated in 24 hr. Pretreatment with propargylglycine, an irreversible inhibitor of cystathionine gamma-lyase, did not abolish the betaine-induced reduction of hepatic glutathione in 4 hr, however, the elevation at t=24 hr was blocked completely. In conclusion the present results indicate that betaine administration induces time-dependent changes on hepatic metabolism of S-amino acids. Betaine enhances metabolic reactions in the methionine cycle, but inhibits cystathionine synthesis and cysteine uptake, leading to a decrease in supply of cysteine for glutathione synthesis. Reduction in glutathione is subsequently reversed due to induction of cysteine synthesis and glutamate cysteine ligase activity.