Protein O-carboxylmethylation in relation to male gamete production and function

Protein O-carboxylmethyltransferase (PCM) activity of differentiating male germ cells in the testis and of spermatozoa is strikingly high. PCM catalyzes the methylesterification by S-adenosylmethionine of dicarboxylic amino acid residues in proteins. PCM appears to be the only type of protein methyltransferase present in mature spermatozoa. Mammalian sperms contain considerable amounts of S-adenosylmethionine and can apparently synthesize this nucleoside from L-methionine and ATP. Spermatozoa are rich in S-adenosylhomocysteine hydrolase. The characteristics of this enzyme in testicular germ cells and in sperms are very similar to those in other mammalian tissues; the very sub-stoichiometric extent of methylation of various pure protein substrates, and the rapid spontaneous hydrolysis of the protein methyl ester products at physiological and especially higher pH values, are particularly remarkable. From studies on processes related to protein O-carboxylmethylation in rat spermatozoa from different regions of the epididymis, and in ejaculated spermatozoa from normal and infertile men, unequivocal evidence could not be obtained for hypotheses of other investigators that PCM-catalyzed reactions are of regulatory importance for the acquisition of a potentiality for motility in sperms during their transit and maturation in the epididymis, or for the locomotion of ejaculated sperms. The findings are discussed in the light of the recent hypothesis of S. Clarke that PCM catalyzes methylesterification of D-aspartyl residues that accumulate in certain proteins as a result of slow spontaneous racemization of L-aspartyl residues, and that the methyl esterification of D-aspartyl residues may be related to disposal or repair of proteins damaged in this fashion.