Metabolic fate of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine by human spermatozoa: biosynthesis and biodegradation.
Human spermatozoa can synthesise 1-alkyl-2-acetyl-glycerophosphocholine (AAGPC) in small amount by acetyltransferase (AT) in absence of any stimulus, but can actively catabolise it by acetylhydrolase (HY). Seminal plasma, on the other hand, was devoid of anabolic enzyme albeit enrich in catabolic enzyme, suggesting as an active site for biodegradation of AAGPC secreted by spermatozoa. Both, AT and HY exhibited pH-optima in range of 7.0-7.6 at which spermatozoa are maximum viable and motile. Ionophore A23187 and EGTA inhibited AT, reversibly, whereas HY was inhibited by BSA, calcium-channel blockers, and phospholipase A2-inhibitors. Effect of aging-time on ejaculates exhibited decreased AT activity with increased HY activity along with unchanged calcium content of spermatozoa. Serotonin in vitro studies showed a pro-aggregator role on agglutination of spermatozoa. Viscid/long liquefaction time ejaculates exhibited raised AT activity and calcium contents with decreased HY activity in spermatozoa and high degree of agglutination. Studies with dithiothreitol-treatment indeed helped in liquefaction but levels of both enzymes remained status quo, suggesting existence of both pathways: remodelling of membrane phospholipids and de novo synthesis of AAGPC in spermatozoa, earlier being pre-dominant. We have proposed a role of AAGPC-Serotonin-Calcium in agglutination and liquefaction of spermatozoa, a vital aspect in normal fertility.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. vibhagujrati@netscape.net
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D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000328:Adult; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000494:pharmacology; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure
D002121:Calcium Channel Blockers; D010972:Platelet Activating Factor; D012701:Serotonin; D000123:Acetyltransferases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D004229:Dithiothreitol