Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-ray crystallographic data show that a specific tetrapeptide aldehyde inhibitor (N-acetylprolylalanylprolylphenylalaninal) forms a stable, covalent, tetrahedral addition complex with the serine protease, SGPA, from Streptomyces griseus. Earlier proposals, based on kinetic measurements, for the covalent nature of such linkages are confirmed, and the difference electron density map of this aldehyde inhibitor indicates that a major conformational change of the histidyl-57 side chain occurs on inhibitor binding.
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PMID:Crystallographic and kinetic investigations of the covalent complex formed by a specific tetrapeptide aldehyde and the serine protease from Streptomyces griseus. 10 92

PSA is a kallikrein-like, serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. PSA is also present in the serum and can be measured reliably by either a monoclonal immunoradiometric assay or a polyclonal radioimmunoassay. The calculated half-life of serum PSA ranges from 2.2 to 3.2 days and the metabolic clearance rate of this tumor marker follows first-order kinetics. Digital rectal examination, cystoscopic examination and prostate biopsy all can cause spurious elevations of the serum PSA concentration. Conditions such as bacterial prostatitis and acute urinary retention also can falsely elevate the serum PSA level. Because approximately 25% of the patients with BPH only will have an elevated serum PSA concentration and BPH tissue contributes to this PSA value in a variable manner from patient to patient, it is unlikely that PSA by itself will become an effective screening tool for the early diagnosis of prostate cancer. However, if combined with digital rectal examination and/or transrectal ultrasound it may become a vital part of any early detection program. Prostatic intraepithelial neoplasia also may be associated with moderately elevated serum PSA levels. Although there is a direct correlation between the serum PSA concentration and clinical stage, PSA is not sufficiently reliable to determine the clinical stage on an individual basis. This finding also applies to pathological stage. As a result, the preoperative serum PSA concentration cannot be used to decide whether to recommend radical prostatectomy for potential cure. Low preoperative serum PSA concentrations in patients with previously untreated prostate cancers are predictive of a negative bone scan. Thus, in these select patients a staging bone scintigram may not be necessary. With respect to monitoring patients after definitive therapy, PSA is an exquisitely sensitive tumor marker. Irrespective of the treatment modality (radical prostatectomy, radiation therapy or antiandrogen treatment), PSA reflects accurately the tumor status of the patient and is prognostic of eventual outcome; this tumor marker is capable of predicting tumor recurrence months before its detection by any other method. PSA is also a most useful immunocytochemical marker. Its sensitivity and specificity to identify tissue of prostatic origin approach 100%. When compared to PAP, PSA is a more precise and meaningful marker in all clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. 170 89

PSA is a 34-kd 240-amino acid glycoprotein produced by the prostatic epithelial cells. It is a member of the glandular kallikrein gene family and has a high sequence homology with human glandular kallikrein (hGK-1). PSA is a serine protease and has chymotrypsin-, trypsin-, and esterase-like activities. It is secreted into the seminal fluid where it degrades two seminal vesicle proteins that are important components of the semen coagulum, thus playing an important role in semen liquefaction. The production of PSA protein appears to be under the control of circulating androgens acting through the androgen receptor. Therefore, the significance of a low serum PSA value in a patient who has undergone previous antiandrogen therapy may not be the same as that for a patient who has not received endocrine treatment.
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PMID:Prostate-specific antigen and prostatic acid phosphatase: biomolecular and physiologic characteristics. 171 6

Human seminal vesicle and prostatic fluids were obtained separately and reconstituted in vitro to test the hypothesis that proteolytic enzymes of prostatic origin would degrade seminal vesicle-specific antigen (SVSA). Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis to follow the fate of SVSA over time, we found that upon mixing the two secretions, SVSA was converted to forms of intermediate and low molecular weight identical to transformations seen in normal liquefied ejaculates. Diisoproprylfluorophophate, a serine protease inhibitor, prevented this degradation, indicating serine protease involvement in the proteolysis of SVSA. Prostate-specific antigen (PSA; also known as P-30), recently identified as a serine protease, was examined for its ability to mimic the effects of prostatic fluid on SVSA. Purified PSA catalyzed degradation of SVSA to produce proteolytic fragments that comigrated and were immunologically related to SVSA fragments produced by prostatic fluid. Purified PSA in the presence of serine protease inhibitors was unable to degrade SVSA. These results demonstrate that SVSA is a substrate for PSA during human semen liquefaction.
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PMID:Human seminal vesicle-specific antigen is a substrate for prostate-specific antigen (or P-30). 246 Jan 48

Prostate specific antigen is an abundant prostate-derived serine protease in the seminal fluid. Low concentrations of the protein are normally released into blood, but above normal concentrations are frequently detected in prostate disease. The PSA-ACT complex is the predominant molecular form of serum PSA (up to approximately 95%) although complex formation is slow between the purified proteins in vitro. A free, noncomplexed form of PSA constitutes a minor fraction of the serum PSA, although serum ACT occurs in large molar excess. The free, noncomplexed form of serum PSA is reported to constitute a significantly smaller proportion of the PSA in untreated prostate cancer than in BPH. The molecular basis for this finding is unclear, but measurements of the proportion of the free form of serum PSA or the proportion of serum PSA-ACT may facilitate discrimination between prostate cancer and BPH.
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PMID:Significance of different molecular forms of serum PSA. The free, noncomplexed form of PSA versus that complexed to alpha 1-antichymotrypsin. 750 76

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.
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PMID:Prostatic specific antigen. 753 74

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 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).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemistry of prostate specific antigen, PSA. 754 81

The precursor or zymogen form of prostate-specific antigen (pro-PSA) is composed of 244 amino acid residues including an amino-terminal propiece of 7 amino acids. Recombinant pro-PSA was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified. The zymogen was readily activated by trypsin at a weight ratio of 50:1 to generate PSA, a serine protease that cleaves the chromogenic chymotrypsin substrate 3-carbomethoxypropionyl-L-arginyl-L-prolyl-L-tyrosine-p-nitroanili ne- HCl (S-2586). In this activation, the amino-terminal propiece Ala-Pro-Leu-Ile-Leu-Ser-Arg was released by cleavage at the Arg-Ile peptide bond. The recombinant pro-PSA was also activated by recombinant human glandular kallikrein, another prostate-specific serine protease, as well as by a partially purified protease(s) from seminal plasma. The recombinant PSA was inhibited by alpha1-antichymotrypsin, forming an equimolar complex with a molecular mass of approximately 100 kDa. The recombinant PSA failed to activate single chain urokinase-type plasminogen activator, in contrast to the recombinant hK2, which readily activated single chain urokinase-type plasminogen activator. These results indicate that pro-PSA is converted to an active serine protease by minor proteolysis analogous to the activation of many of the proteases present in blood, pancreas, and other tissues. Furthermore, PSA is probably generated by a cascade system involving a series of precursor proteins. These proteins may interact in a stepwise manner similar to the generation of plasmin during fibrinolysis or thrombin during blood coagulation.
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PMID:Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein. 926 Nov 79

Prostate specific antigen is a highly specific marker of prostatic tissue. Recent studies have shown, that it is present in several other human tissues, tumors and fluids. PSA has been identified as a serine protease and member of the kallikrein family of enzymes. In our study PSA concentration was measured in 97 cytosols of breast cancer tissues and 14 samples, prepared from human endometrium. Cytosols were analysed also for steroid hormone receptors, EGF-receptor, Cathepsin D and pS-2 protein. PSA was found in 84.5% of breast cancer tissues and in 12 endometrium samples. High concentration of PSA were associated with high pS-2 protein levels. No correlation was found between the concentration of steroid hormone receptors and PSA in our material. The results suggest, that PSA in cytosol of human breast cancer and endometrial tissues may be an additional new prognostic indicator.
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PMID:[Determination of prostate-specific antigen (PSA) in cytosol of breast tumors and human endometrium--new diagnostic approaches]. 961 May 20

The cDNA for the trypsin-like serine protease gene (TLSP, HGMW-approved symbol PRSS20) has been recently identified. TLSP is expressed in brain and skin tissues but little else is known about this new serine protease gene. In this paper, we describe the complete genomic organization and precise mapping of the TLSP gene. This gene spans 5.3 kb of genomic sequence on chromosome 19q13.3-q13. 4. The gene consists of six exons, the first of which is untranslated. All splice junctions follow the GT/AG rule, and the intron phases are identical to those of other kallikrein-like genes, including zyme (PRSS9), NES1 (PRSSL1), and neuropsin (PRSS19). Fine-mapping of the area indicates that TLSP lies downstream from the PSA, zyme, neuropsin, and NES1 genes. Significant sequence homologies were found between TLSP and other human kallikreins. Furthermore, there is conservation of the catalytic triad (histidine, aspartic acid, serine) and of the number of coding exons (five; the same in all members of the kallikrein gene family). We thus suggest that TLSP is a new member of the human kallikrein gene family. TLSP is expressed in many tissues including cerebellum, prostate, salivary glands, stomach, lung, thymus, small intestine, spleen, liver, and uterus. TLSP expression appears to be regulated by steroid hormones in the breast carcinoma cell line BT-474.
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PMID:Genomic organization, mapping, tissue expression, and hormonal regulation of trypsin-like serine protease (TLSP PRSS20), a new member of the human kallikrein gene family. 1066 48


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