棉酚乙酸对NAD连接酶的抑制动力学

Inhibition kinetics of NAD-linked enzymes by gossypol acetic acid.

作者信息

Ikeda M

机构信息

Department of Obstetrics and Gynecology, School of Medicine, Teikyo University, Tokyo, Japan.

出版信息

Andrologia. 1990 Sep-Oct;22(5):409-16. doi: 10.1111/j.1439-0272.1990.tb02019.x.

DOI:10.1111/j.1439-0272.1990.tb02019.x

PMID:2073051

Abstract

Effects of gossypol on human spermatozoal enzymes were investigated. This compound was found to be a potent inhibitor of the NAD-linked enzymes, glucelaldehyde-3-phosphate dehydrogenase (GA3PDH), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). MDH was inhibited by gossypol when the reaction was carried out in malate-oxalacetate (direct) or oxalacetate-malate (reverse) directions. The I50 of gossypol for the direct reaction was 2.9 microM, whereas that for the reverse reaction was 1.2 microM. Reciprocal plots due to Lineweaver-Burk showed that MDH is inhibited in a noncompetitive manner with respect to both reactions. LDH was also inhibited by this compound when pyruvate or alpha-ketobutyrate was used as a substrate. Gossypol was a noncompetitive inhibitor for LDH. The I50 of gossypol for LDH were 9.8 microM and 11.3 microM, when using pyruvate and alpha-ketobutyrate, respectively as substrates. The I50 of gossypol for GA3PDH and ICDH were 110 microM and 2.7 microM, respectively.

摘要

研究了棉酚对人类精子酶的影响。发现该化合物是烟酰胺腺嘌呤二核苷酸（NAD）连接酶的有效抑制剂，这些酶包括3 - 磷酸甘油醛脱氢酶（GA3PDH）、乳酸脱氢酶（LDH）、苹果酸脱氢酶（MDH）和异柠檬酸脱氢酶（ICDH）。当反应在苹果酸 - 草酰乙酸（正向）或草酰乙酸 - 苹果酸（反向）方向进行时，MDH受到棉酚的抑制。棉酚对正向反应的半数抑制浓度（I50）为2.9微摩尔，而对反向反应的I50为1.2微摩尔。Lineweaver - Burk双倒数作图表明，MDH在这两个反应中均以非竞争性方式受到抑制。当使用丙酮酸或α - 酮丁酸作为底物时，LDH也受到该化合物的抑制。棉酚是LDH的非竞争性抑制剂。当分别使用丙酮酸和α - 酮丁酸作为底物时，棉酚对LDH的I50分别为9.8微摩尔和11.3微摩尔。棉酚对GA3PDH和ICDH的I50分别为110微摩尔和2.7微摩尔。