Inhibition of gamma-glutamyl hydrolases in human cells by 2-mercaptomethylglutaric acid.
Inhibition of gamma-glutamyl hydrolases in human cells by 2-mercaptomethylglutaric acid.
复制标题
2-巯基甲基戊二酸抑制人体细胞中的 γ-谷氨酰水解酶。
DOI：
10.1016/s0006-291x(87)80509-0
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发表时间：
1987
影响因子：
3.1
通讯作者：
Vuchich,MJ
中科院分区：
文献类型：
--
作者：
Whitehead,VM;Kalman,TI;Vuchich,MJ
Cultured human lymphocytes and fibroblasts accumulate methotrexate during 24 hours and synthesize methotrexate polyglutamates up to the hexaglutamate, with the triglutamate predominating. In the interval after incubation with methotrexate, drug is lost, metabolites are converted to longer chain-lengths, and methotrexate pentaglutamate predominates. 2-Mercaptomethyl-glutaric acid, an inhibitor of neutral pH gamma-glutamyl hydrolasesin vitro, had little effect on polyglutamate synthesis during incubation of the cells with methotrexate, but maintained for 48 hours almost all the methotrexate as the pentaglutamate when added after the removal of the drug. These findings demonstrate that inhibition of gamma-glutamyl hydrolases is an effective approach to alter the distribution of polyglutamate forms of methotrexatein vivoand indicate that enzymatic hydrolysis may contribute to regulation of polyglutamate chain lengths in human cells.
