Biochemistry of prostate specific antigen, PSA

• Human prostate specific antigen, PSA, is a product of the human glandular kallikrein gene locus on chromosome 19 that is almost selectively expressed by prostate tissue. PSA is one of the dominating prostate derived proteins in seminal fluid. The mature form of PSA, a single chain glycoprotein of 237 amino acids, is a serine protease manifesting restricted chymotrypsin-like activity. PSA is mainly responsible for gel dissolution in freshly ejaculated semen by proteolysis of the major gel forming proteins, semenogelin I and II, and fibronectin. In semen approximately two thirds of PSA is enzymatically active. The remaining 30 - 40% is inactive due to internal cleavage(s). A few per cent of PSA in semen is complexed to the protein C inhibitor. PSA complexed to α1-antichymotrypsin (ACT) constitutes the predominant molecular form of serum PSA, although complex formation is slow between the purified proteins in vitro. PSA also forms stable complexes with α2-macroglobulin in vitro but as this results in encapsulation of PSA and complete loss of the PSA-epitopes, the in vivo significance of this complex formation is presently unclear. A free, non-complexed form of PSA constitutes a minor fraction of the serum PSA despite the large molar excess of antiproteasees such as ACT. In patients with carcinoma of the prostate the serum PSA level increases. Analysis of the serum level of PSA is used both for diagnosing and monitoring patients with carcinoma of the prostate (CAP). These can now more efficiently be distinguished from subjects with benign hyperplasia of the prostate (BPH) alone, who often also have increased concentrations of PSA in serum, by specific measurements of the individual forms of PSA in serum. Patients with CAP have a higher ratio of PSA-ACT complexes to total PSA in serum than BPH subjects and a lower ratio of free to total PSA.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

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