Mechanism of action of (-)gossypol on ATP production in isolated hamster spermatids.
The ATP content of round spermatids isolated from hamsters was decreased 90% after 18 h of incubation in the presence of 4 microM-(-)gossypol and 0.10% bovine serum albumin (BSA). The (+)-enantiomer had no effect under these incubation conditions. The Michaelis-Menten constant Km and the maximal initial velocity Vmax of cellular LDH-C4 were not significantly altered after 18 h of incubation of the spermatids with (-)gossypol. Furthermore, there was no effect of (-)gossypol on the production of 14CO2 from L-[U-14C]lactate. It is concluded that (-)gossypol does not inhibit ATP production in spermatids by an effect on the sperm-specific LDH-C4 enzyme or on the mitochondrial oxidation of pyruvate. Rather, (-)gossypol may have an effect on the coupling between electron transport and ATP synthesis in the mitochondria. This action of (-)gossypol may not involve the H+-conducting activity of gossypol, but could be produced through binding of (-)gossypol to specific mitochondrial proteins.
Den Boer
P J
PJ
Department of Biochemistry II, Erasmus University Rotterdam, The Netherlands.
Grootegoed
J A
JA
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D006072:Gossypol / Q000494:pharmacology*; D007527:Isoenzymes; D007536:Isomerism; D007770:L-Lactate Dehydrogenase / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008297:Male; D008647:Mesocricetus; D013087:Spermatids / Q000187:drug effects / Q000378:metabolism*
D007527:Isoenzymes; D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D006072:Gossypol