Jung Young S, Kwak Hye E, Choi Kwon H, Kim Young C
Seoul National University, College of Pharmacy, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, Korea.
Adv Exp Med Biol. 2003;526:245-52. doi: 10.1007/978-1-4615-0077-3_31.
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.
在腹腔注射单剂量乙醇（3 g/kg）的雄性大鼠中，研究了含硫氨基酸肝脏代谢的变化。乙醇给药后，肝脏中蛋氨酸和S-腺苷同型半胱氨酸（SAH）的浓度升高，但S-腺苷甲硫氨酸（SAM）、半胱氨酸和谷胱甘肽（GSH）迅速下降。蛋氨酸腺苷转移酶（MAT）、胱硫醚β-合酶（CβS）和胱硫醚γ-裂合酶（CγL）的活性均受到抑制。γ-谷氨酰半胱氨酸合成酶（GCS）的活性从t = 8小时开始升高，但肝脏谷胱甘肽（GSH）水平在48小时内未恢复到对照水平。肝脏中牛磺熊去氧胆酸和牛磺酸水平立即升高，从t = 18小时开始降至对照水平以下。血清中牛磺酸浓度的变化与肝脏中观察到的结果一致。半胱氨酸双加氧酶（CDO）的活性迅速升高，但从t = 24小时开始下降。结果表明，急性剂量的乙醇会引起肝脏中含硫氨基酸代谢的显著变化。乙醇不仅通过抑制转硫反应，还通过增强其经由牛磺熊去氧胆酸向牛磺酸的不可逆分解代谢，来降低用于谷胱甘肽合成的半胱氨酸可用性。讨论了这一发现的生理学意义。
