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.
Jones
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Department of Medicine, Madigan Army Medical Center, Tacoma, Washington 98431.
Plymate
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D003066:Coenzyme A Ligases / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008042:Linolenic Acids / Q000494:pharmacology*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013094:Spermatozoa / Q000378:metabolism*; D013229:Stearic Acids / Q000494:pharmacology*; D017962:alpha-Linolenic Acid; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D008042:Linolenic Acids; D010169:Palmitic Acids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013229:Stearic Acids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid; C031183:stearic acid; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase