Mechanism-based approaches to inhibition of the synthesis and degradation of folate and antifolate polyglutamates.
Mechanism-based approaches to inhibition of the synthesis and degradation of folate and antifolate polyglutamates.
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基于机制的方法来抑制叶酸和抗叶酸聚谷氨酸的合成和降解。
DOI：
10.1007/978-1-4615-2960-6_132
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发表时间：
1993
影响因子：
--
通讯作者：
Kalman,TI
中科院分区：
文献类型：
--
作者：
Kalman,TI
Tetrahydrofolate and its one-carbon coenzyme derivatives undergo in the cell polyglutamylation, which is essential for their cellular retention and optimal enzymatic activity.1,2The biological activity of glutamate-containing “classical” antifolates also depends on the extent of their intracellular poly-γ-glutamylation. Cells unable to polyglutamylate these antifolates are resistant to the cytotoxicity of these drugs. While the importance of polyglutamate chain length has been clearly demonstrated, the regulatory role of the enzymes responsible for the synthesis and breakdown of the poly-γ-glutamyl chain, fblylpolyglutamate synthetase (FPGS) and γ-glutamyl hydrolase (GGH, conjugase), respectively, is poorly understood. Complicating factors are the low rate of chain elongation and shortening compared to other coenzyme metabolizing activities and the tissue-to-tissue, cell-to-cell and subcellular variation of GGH activities associated with different proteins.1,2
