Inhibition kinetics of NAD-linked enzymes by gossypol acetic acid.
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.
Ikeda
M
M
Department of Obstetrics and Gynecology, School of Medicine, Teikyo University, Tokyo, Japan.
D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D009243:NAD / Q000378:metabolism*; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000494:pharmacology; D013094:Spermatozoa / Q000187:drug effects / Q000201:enzymology*
D013089:Spermatocidal Agents; D009243:NAD; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006072:Gossypol; C028178:gossypol acetic acid