BIOCHEMISTRY OF PROSTATE-SPECIFIC ANTIGEN, PSA

BIOCHEMISTRY OF PROSTATE-SPECIFIC ANTIGEN, PSA
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DOI:
10.3109/00365519509090559
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发表时间:
1995-01-01
影响因子:
2.1
通讯作者:
LILJA, H
LILJA, H
中科院分区:
医学4区
文献类型:
--
作者:
MALM, J;LILJA, H

文献摘要

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人前列腺特异性抗原PSA是位于19号染色体上的人腺激肽释放酶基因座的产物,其几乎由前列腺组织选择性表达。前列腺特异性抗原(PSA)是精液中主要的前列腺源性蛋白质之一。PSA的成熟形式是一种237个氨基酸的单链糖蛋白,是一种丝氨酸蛋白酶,表现出有限的胰凝乳蛋白酶样活性。PSA主要负责新鲜精液中的凝胶溶解,其通过主要凝胶形成蛋白、精液凝固蛋白I和II以及纤连蛋白的蛋白水解来实现。在精液中,大约三分之二的PSA具有酶活性。剩余的30-40%由于内部裂解而无活性,精液中有百分之几的PSA与蛋白C抑制剂复合。与α(1)-抗胰凝乳蛋白酶(ACT)复合的PSA构成血清PSA的主要分子形式,尽管体外纯化蛋白质之间的复合物形成缓慢。PSA还在体外与α 2-巨球蛋白形成稳定的复合物,但由于这导致PSA的包封和PSA表位的完全丧失,因此这种复合物形成的体内意义目前尚不清楚。游离的、非复合形式的PSA构成血清PSA的一小部分,尽管抗蛋白水解酶如ACT的摩尔过量很大。前列腺癌患者血清PSA水平升高。血清PSA水平的分析用于诊断和监测患有前列腺癌(CAP)的患者。通过对血清中PSA的个体形式进行特异性测量,现在可以更有效地将这些与仅患有良性前列腺增生(BPH)的受试者区分开,所述BPH受试者通常也具有血清中PSA浓度增加。CAP患者血清中PSA-ACT复合物与总PSA的比值高于BPH患者,而游离PSA与总PSA的比值低于BPH患者。
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 alpha(1)-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 alpha(2)-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 antiproleasees 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.