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.
Jung
Young S
YS
Seoul National University, College of Pharmacy, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, Korea.
Kwak
Hye E
HE
Choi
Kwon H
KH
Kim
Young C
YC
D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000096:biosynthesis*
D000603:Amino Acids, Sulfur; D013654:Taurine; D000431:Ethanol; D005978:Glutathione; D003545:Cysteine