Jung Young S, Kim Sun J, Kwon Do Y, Kim Young C
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
Biochem Biophys Res Commun. 2008 Apr 18;368(4):913-8. doi: 10.1016/j.bbrc.2008.02.005. Epub 2008 Feb 12.
Alterations in hepatic transsulfuration reactions were determined in rats treated with a glutathione-depleting agent. A dose of l-buthionine-(S,R)-sulfoximine decreased hepatic methionine, cysteine, S-adenosylmethionine, and glutathione levels rapidly. Methionine adenosyltransferase and gamma-glutamylcysteine lygase activities were decreased transiently, but significantly. The activity of cysteine dioxygenase was increased, resulting in an elevation of hypotaurine and taurine concentrations. Administration of phorone reduced hepatic glutathione and cysteine similarly, but S-adenosylmethionine concentrations were elevated for as long as 72h. Hepatic methionine adenosyltransferase, cystathionine beta-synthase, cystathionine gamma-lyase, and gamma-glutamylcysteine lygase activities were all increased but cysteine dioxygenase activity and taurine generation were markedly depressed. The results show that a decrease in hepatic GSH induces profound changes in sulfur amino acid metabolomics, which would subsequently influence various cellular processes. It is suggested that the change in hepatic levels of sulfur-containing substances and its physiological significance should be considered when a glutathione-depleting agent is utilized in biological experiments.
在用谷胱甘肽耗竭剂处理的大鼠中测定了肝脏转硫反应的变化。一剂L-丁硫氨酸-（S，R）-亚砜亚胺迅速降低了肝脏中甲硫氨酸、半胱氨酸、S-腺苷甲硫氨酸和谷胱甘肽的水平。甲硫氨酸腺苷转移酶和γ-谷氨酰半胱氨酸连接酶活性短暂但显著降低。半胱氨酸双加氧酶的活性增加，导致次牛磺酸和牛磺酸浓度升高。给予佛波酯同样降低了肝脏中的谷胱甘肽和半胱氨酸，但S-腺苷甲硫氨酸浓度在长达72小时内升高。肝脏中甲硫氨酸腺苷转移酶、胱硫醚β-合酶、胱硫醚γ-裂合酶和γ-谷氨酰半胱氨酸连接酶的活性均增加，但半胱氨酸双加氧酶活性和牛磺酸生成明显受到抑制。结果表明，肝脏中谷胱甘肽的减少会引起硫氨基酸代谢组学的深刻变化，这随后会影响各种细胞过程。建议在生物学实验中使用谷胱甘肽耗竭剂时，应考虑肝脏中含硫物质水平的变化及其生理意义。
