Evidence for the regulation of fatty acid utilization in human sperm by docosahexaenoic acid.

The effects of stearic (18:0), linolenic (18:3), and docosahexaenoic (22:6) acids on palmitoyl coenzyme A (CoA) formation by a long-chain fatty acid:CoASH ligase (adenosine monophosphate) (E. C. 6.2.1.3-enriched fraction from human spermatozoa were studied. Both 18:0 and 18:3 were competitive inhibitors for palmitic (16:0) acid activation with Kis of 17.7 and 5.7 microM, respectively. In contrast, 22:6 was a noncompetitive inhibitor demonstrating a Ki of 9.5 microM. These data coupled with previous studies support the conclusion that 16:0, 18:0, and 18:3 and other saturated and unsaturated fatty acids are activated by the same ligase enzyme in sperm. Although the kinetics and interactions of 22:6 are unique compared to the other fatty acids found in sperm phospholipids, we cannot discern from our data if it is activated by a separate enzyme. We propose that 22:6, or a metabolite of 22:6, may regulate free fatty acid utilization in human sperm and that this hypothesis may provide an enzymatic explanation for the changes observed in phospholipid-bound fatty acids during the epididymal maturation of sperm.