S NITROSOGLUTATHIONE AS SUBSTRATE FOR GAMMA GLUTAMYL TRANSPEPTIDASE

S 亚硝基谷胱甘肽作为 γ 谷氨酰转肽酶的底物

• 批准号: 6307863
• 负责人: NEIL HOGG
• 金额: $ 1.13万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6307863
• 关键词: bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; cardiovascular system; enzymes

S-Nitrosoglutathione (GSNO) has been used as a nitric oxide donor compound and has also been postulated to be involved in the transport of nitric oxide in vivo. In this study we have examined the possibility that GSNO is a substrate for gamma-glutamyl transpeptidase (gamma-GT), an enzyme that hydrolyses the gamma-glutamyl moiety of glutathione to give glutamate and cysteinylglycine. gamma-GT accelerated the decomposition of GSNO, forming S-nitrosocysteinylglycine (CG-SNO) by a mechanism inhibitable by the gamma-GT inhibitors acivicin and S-methylglutathione. The Km of gamma-GT for GSNO was found to be 28 micromole. In the presence of contaminating transition metal ions, gamma-GT accelerated the release of nitric oxide from GSNO, as CG-SNO is more susceptible to transition metal ion-dependent decomposition than GSNO. However, in the presence of the transition metal ion chelator diethylenetriaminepentaacetic acid, neither GSNO nor CG-SNO decomposed to generate nitric oxide. Neither S-methylglutathione nore acivicin affected the vasodilatory response to GSNO in an isolated perfused rat heart. However, rat kidney homogenate stimulated the decomposition of GSNO by an acivicin-inhibitable mechanism. It is likely therefore that gamma-GT is involved in the decomposition of GSNO in the kidney but not in the heart.

S-亚硝基谷胱甘肽(GSNO)已被用作一氧化氮供体 化合物，也被推定参与了运输 体内一氧化氮的含量。在这项研究中，我们检查了 GSNO作为γ-谷氨酰转肽酶底物的可能性 (伽马-谷氨酰转氨酶)，一种能分解谷氨酰基部分的酶 谷胱甘肽提供谷氨酸和半胱氨酸甘氨酸。Gamma-GT 加速GSNO的分解，形成 S亚硝基半胱氨酸甘氨酸(CG-SNO)的抑制机制 伽玛-谷氨酰转氨酶抑制剂阿维菌素和S-甲基谷胱甘肽。里程数 GSNO的伽马-GT为28微摩尔。在……面前 污染过渡金属离子的伽马-GT加速释放 来自GSNO的一氧化氮，因为CG-SNO更容易转变 比GSNO依赖于金属离子的分解。然而，在现场 过渡金属离子螯合剂二乙三胺五乙酸二乙酯的研究 酸，GSNO和CG-SNO都不分解生成一氧化氮。 S-甲基谷胱甘肽和阿昔维辛均不影响血管扩张 GSNO对离体灌流大鼠心脏的反应。但是，Rate 肾匀浆对An诱导GSNO分解的影响 阿维菌素的抑制机制。因此，伽马-GT很可能 参与GSNO在肾脏中的分解，但不参与GSNO在肾脏的分解 心。