Kinetic characterization of the inhibition of purified cynomolgus monkey lactate dehydrogenase isozymes by gossypol.
Kinetic characterization of the inhibition of purified cynomolgus monkey lactate dehydrogenase isozymes by gossypol.
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棉酚抑制纯化食蟹猴乳酸脱氢酶同工酶的动力学特征。
DOI：
10.1002/j.1939-4640.1986.tb00946.x
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发表时间：
1986
影响因子：
--
通讯作者：
Hoskins,DD
中科院分区：
文献类型：
--
作者：
Stephens,DT;Whaley,KJ;Klimkow,NM;Goh,P;Hoskins,DD
This report describes the results of the first step in a sequence of experiments designed to test the hypothesis that the sperm‐specific isozyme of lactate dehydrogenase (LDH‐C4), is a site of action of the potential male contraceptive agent gossypol. Cynomolgus monkey LDH‐A4, LDH‐B4, and LDH‐C4were purified and kinetically characterized. LDH‐A4and LDH‐B4exhibited “linear mixed‐type” inhibition by gossypol with both lactate and pyruvate as variable substrates. LDH‐C4also exhibited “linear mixed‐type” inhibition with lactate as substrate. However, the C4isozyme exhibited “parabolic mixed‐type” inhibition by gossypol and substrate inhibition with pyruvate as substrate, the latter due to abortive complex formation. Of the three isozymes, LDH‐C4exhibited the lowest apparent Kmfor pyruvate and the highest apparent Kmfor lactate. The LDH‐C4form was found to be the most sensitive isozyme to gossypol inhibition, since it had the lowest apparent K1values for gossypol inhibition. The effect of gossypol on coenzyme binding to LDH‐C4was examined and gossypol binding was found to inhibit binding and release of NADH but not NAD+, an effect possibly due to its interaction with the more hydrophobic loop region of LDH‐C4.
