Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors.
Prostate-specific antigen (PSA) is one of the three most abundant prostatic-secreted proteins in human semen. It is a serine proteinase that, in its primary structure, manifests extensive similarities with that of the Arg-restricted glandular kallikrein-like proteinases. When isolated from semen by the addition of chromatography on aprotinin-Sepharose to a previously described procedure, PSA displayed chymotrypsin-like activity and cleaved semenogelin and the semenogelin-related proteins in a rapid and characteristic pattern, but had no trypsin-like activity. About one third of the purified protein was found to be enzymatically inactive, due to cleavage carboxy-terminal of Lys145. Active PSA formed SDS-stable complexes with alpha 1-antichymotrypsin, alpha 2-macroglobulin-analogue pregnancy zone protein. PSA formed inhibitory complexes with alpha 1-antichymotrypsin at a molar ratio of 1:1, a reaction in which PSA cleaved the inhibitor in a position identical to that reported from the reaction between chymotrypsin and alpha 1-antichymotrypsin. The formation of stable complexes between PSA and alpha 1-antichymotrypsin occurred at a much slower rate than that between chymotrypsin and alpha 1-antichymotrypsin, and at a similar or slightly slower rate than that between PSA and alpha 2-macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with alpha 2-macroglobulin and alpha 1-antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
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A
Christensson
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CB
Laurell
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H
Lilja
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D000951:Antigens, Neoplasm; D015842:Serine Proteinase Inhibitors; D000514:alpha 1-Antichymotrypsin; D000511:alpha-Macroglobulins; D017430:Prostate-Specific Antigen