A bioenergetic model of gossypol action: effects of gossypol on adult rat spermatogenic cells.

Rat spermatogenic cells have glycolytic rates of 124 +/- 36 nmol lactate.mg protein-1.h-1. Maximum glycolytic rates in the absence of oxidative phosphorylation do not exceed the basal rates by greater than 40%. From the rates of oxygen consumption and lactate production it can be calculated that less than 8% of the total ATP produced by spermatogenic cells is provided by glycolysis. These properties of spermatogenic cells would render them highly susceptible to cytotoxicity due to the action of agents like gossypol that impair mitochondrial oxidative phosphorylation or to conditions that produce testicular hypoxia. The main effect of gossypol on spermatogenic cell energy metabolism is to uncouple mitochondrial oxidative phosphorylation. In the absence of glucose, this uncoupling action of gossypol would change the NAD+/NADH redox coupling and, consequently, could modify metabolic fluxes through the lactic dehydrogenase catalyzed reaction.