The aspartic proteases (ED 3.4.23) are a widespread group of enzymes in mammals, avia, invertebrates, fungi, bacteria, virus and plants. They are synthesized as stable inactive proenzymes and are activated at low pH. Most aspartic proteases exert a broad general proteolytic activity with the only known exception of renin that has an extreme specificity and function at neutral pH. In mammals, there are two sets of pepsinogens (pepsinogen A; EC 184.108.40.206 and pepsinogen C, EC 220.127.116.11). They are immunologically distinquishable and have approx 70% homology in amino acid sequence. Human pepsinogen A consists of 5 isoenzymes coded by 3 different genes on chromosome 11. Human pepsinogen C consist of 3 isoenzymes, but only one gene on chromosome 6 has been reported. Semen of higher primates contain high concentration of pepsinogen C. Among the 3 isoenzymes of human pepsinogen C, the 2 with fastest electrophoretic mobility are in semen. Apparent immunological identity is noted between seminal and gastric pepsinogen C with polyclonal antibodies. We have not been able to distinguish the two enzymes by amino acid composition and the 28 N-terminal amino acid residues of the proenzyme are identical. We have raised a monoclonal antibody that is able to recognize a non-carbohydrate antigenic determinant only present in seminal pepsinogen C indicating a molecular difference. The pH of ejaculated human semen is 7.2 - 7.4. At this range, pepsinogen is stable with no activation. Since vaginal pH is 3.5 to 5.2, activation/enzymatic function of seminal pepsinogen C takes place in acidic environment of the vagina. Physiological functions in fertilization like proacrosin activation is suggested.
|Status||Udgivet - 1 dec. 1989|