Enzyme prostate-specific antigen

The EDTA-Tb3+ complex is poorly luminescent, but becomes strongly emissive when it forms a ternary complex with salicylic acid. By using alkaliphosphatase (ALP) as the label of the antibody, a unique immunoassay system specific to Tb3+ was constmcted (fig. 11) by Evangelista et al. (1991) and Christopoulos et al. (1992). The enzyme ALP cleaves the phosphoester bond of the substrate and releases 5-fluorosalicylic acid, which binds to EDTA-Tb3+ and sensitizes luminescence from Tb3+. This method is employed for the determination of semm AFP (cx-fetoprotein) and PSA (prostate-specific antigen). 

Forensic biochemists perform blood typing and enzyme tests on body fluids in cases involving assault, and also in paternity cases. Even tiny samples of blood, saliva, or semen may be separated by electrophoresis and subjected to enzymatic analysis. In the case of rape, traces of semen found on clothing or on the person become important evidence the composition of semen varies from person to person. Some individuals excrete enzymes such as acid phosphatase and other proteins that are seldom found outside seminal fluid, and these chemical substances are characteristic of their semen samples. The presence of semen may be shown by the microscopic analysis for the presence of spermatozoa or by a positive test for prostate specific antigen. 

Phage libraries have also been used to study the substrate specificity of enzymes by finding an improved artificial substrate. Coombs et al. (69) reported the detailed assessment of specificity for a serine protease belonging to the a-chymotrypsin family, the prostate specific antigen (PSA). They used both substrate optimization by singlepoint mutations and phage display libraries. The sequence of the 14-member substrate 10.2 (70) was used to start the iterative optimization process (Fig. 10.11) in which substitution or exchange of the PI, P2, or P2 residues increased the substrate affinity... 

Other enzymes are also useful indices of liver pathology. Serum alkaline phosphatase is often a useful indicator of liver and bone disease. The alkaline phosphatases are a diverse group of enzymes that catalyze reactions in which a phosphate is removed from a phosphate ester, especially at an alkaline pH. Physicians don t care about this. They do care that serum alkaline phosphatase levels often rise with bone breakdown (as in tumor infiltration) and in liver disease, especially where tliere is obstruction of the bile duct. Acid phosphatase is particularly rich in the prostate. A rise in its serum levels provides a test as to the presence of prostate carcinoma. This test has largely been replaced by assay for Prostate Specific Antigen (PSA), a serine protease that is elevated in prostatic carcinoma. 

Prostate-specific antigen Enzyme that liquefies the seminal coagulum Present in rare basal cells mainly in secretory luminal cells... 

With few exceptions, an increase in the activity or mass of an enzyme or isoenzyme is not specific or sensitive enough to be used for identifying the type of cancer or the specific organ involvement. An exception is PSA. PSA has mild protease activity and amino acid sequence homology with serine protease of the kallikrein family.It is expressed by normal, benign, hyperplastic, and cancerous prostate glands and minimally by other tissue. Until the application of PSA as a marker for prostate cancer, tumor enzymes had lost most of their popularity for use as cancer markers. Enzymes were used historically as tumor markers before the discovery of oncofetal antigens and the advent of monoclonal antibodies. The abnormalities of enzymes as a marker for cancer are either the expression of the fetal form of the enzyme (isozyme) or the ectopic production of enzymes. 

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