来自耐甲氨蝶呤干酪乳杆菌的二氢叶酸还原酶对氧化型叶酸的还原作用

Reduction of oxidised folates by dihydrofolate reductase from methotrexate-resistant Lactobacillus casei.

作者信息

McIntyre L J, Harding N G

出版信息

Biochim Biophys Acta. 1977 Jun 10;482(2):261-71. doi: 10.1016/0005-2744(77)90240-6.

DOI:10.1016/0005-2744(77)90240-6

PMID:18181

Abstract

The use of alternative substrates by dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) was investigated as a possible mechanism for the resistance of Lactobacillus casei to the cytotoxic drug methotrexate. The reduction of folic acid and 10-formylfolic acid by homogeneous enzyme was compared to that of the normal substrate, dihydrofolic acid. The three substrates have different pH optima and Km values. In addition, it was found that the reduction of 10-formylfolic acid was markedly stimulated by the presence of ions. Although the reduction was sensitive to methotrexate in all cases, the ion activation may be of importance in partially inhibited systems.

摘要

研究了二氢叶酸还原酶（5,6,7,8-四氢叶酸：NADP+氧化还原酶，EC 1.5.1.3）使用替代底物作为干酪乳杆菌对细胞毒性药物甲氨蝶呤耐药的一种可能机制。将纯酶对叶酸和10-甲酰叶酸的还原作用与正常底物二氢叶酸的还原作用进行了比较。这三种底物具有不同的最适pH值和Km值。此外，发现离子的存在显著刺激了10-甲酰叶酸的还原。尽管在所有情况下还原作用对甲氨蝶呤都敏感，但离子激活在部分受抑制的系统中可能很重要。

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