Prostatic phosphatase and

Abul-Fadl and King (Al, A2, A3, A4) also investigated the effect of various ions and organic compounds on the acid phosphatase activity of these two tissues. Without describing the results in detail, some of the outstanding effects may be noted. A concentration of 0.5 X 10 M Cu inhibited erythrocytic phosphatase to the extent of 88-96%, but prostatic phosphatase only to the extent of 10-18%. Similarly, 0.5% formaldehyde inhibited completely the erythrocytic phosphatase, but had no effect on prostatic phosphatase. The reverse patterns were shown by 0.5 X 10 M Fe + (ferric) ion, which inhibited erythrocytic phosphatase slightly, about 5-9%, and inhibited the prostatic enzyme to the extent of 80%. Fluoride in 0.01 Af concentration also had comparatively little effect (8% inhibition) on erythrocytic phosphatase but exerted a marked inhibition, 96%, on prostatic phosphate. Of various organic radicals tested, only L-( + )-tartrate (0.01 A/) had a marked differential effect, with 94% inhibition of the prostatic phosphatase and none of the erythrocytic phosphatase. 

Ribonucleic acid is thought to possess a highly branched structure. Cleavage about a branch point in the manner illustrated in (VIII) would give the pyrimidine nucleoside diphosphates discussed above. Ribonucleic acid also contains a number of phospho-monoester end groups which are susceptible to acid prostatic phosphatase and certain other monoesterases. A great deal has been learned of ribonucleic acid structure... 

Nucleotidases are phosphatases active against nucleotides, and such activity is widely distributed in nature. Among mammalian tissues one may mention alkaline intestinal phosphatase,acid prostatic phosphatase, and alkaline bone phosphatase. None of these preparations are specific for nucleotides, although extracts of prostate dephosphorylate nucleotides at a much faster rate than other esters. Enzymes which act only on nucleotides may occur in these tissues but their existence has not been proved. Several specific nucleotidases will now be discussed. 

Acid- and alkaline phosphatases act on a variety of mono- and multiple phosphate carrying low molecular mass molecules. In addition, they hydrolyze many, but not all, phosphoproteins. They are in use for decades to easily screen for diseases, however, somewhat unspe-cifially. For instance, acid phosphatase is used as biomarker for prostate cancer, and alkaline phosphatase to monitor bone (de-) mineralization and liver tumors. 

Red blood cells also contain sufficient acid phenylphospha-tase for mild hemolysis to cause false elevations. Therefore, inhibitors such as ethanol, formaldehyde, copper sulfate> and 1-tartrate have been used to inhibit selectively the enzyme of one or more tissues and enhance the specificity of the test (101). Ethanol is unsuitable because it inhibits the enzyme from erythrocytes and prostate simultaneously, and because it yields serum activities which correlate poorly with prostatic disease. Formaldehyde inhibits the erythrocytic enzyme and has been said to yield clinically satisfactory results. The copoper resistant acid phosphatase of serum is elevated by metastatic carcinoma of the breast, as well as by other metastatic cancers, and is also elevated by a wide variety of non-cancerous diseases. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

Schwartz, M. R. Greenberg, E. and Bodansky, 0. Comparative values of phosphatases and other serum enzymes in following patients with prostatic carcinoma. Cancer (1963), 16, 583-594. 

Acid phosphatase (acid phosphomonoesterase, EC 3.1.3.2) also catalyzes the hydrolysis of phosphoric acid monoesters but with an acidic pH optimum. It has broad specificity and catalyzes transphosphorylations. Acid phosphatases are a quite heterogeneous group with monomeric, dimeric, larger glycoprotein, and membrane-bound forms. Acid phosphatase activity is present in the heart, liver, bone, prostate, and seminal fluid. Prostate carcinomas produce large quantities of acid phosphatase, and the enzyme is, therefore, used as a biomarker [141]. 

A circadian variation in serum acid phosphatase has been reported in patients with prostatic carcinoma and phosphatase activity determined with phenyl phosphatase as substrate (DIO). The nocturnal values decreased 25-50% of the highest day time activity. The highest values were observed from 9 am to 3 pm and the lowest between 9 pm and 3 am. In one patient observations were made at hourly intervals. The peak of 14.2 King-Armstrong units was observed at 11 am and the lowest activity, 6.4 units, at midnight. Orchiectomy did not eliminate the variation. 

Study of intermittent effluxes of acid phosphatase activity in the urine of mature human males 29) led to the discovery of the enzyme in semen and prostate by Kutscher and Wolberg (S). The enzyme is very active in human prostatic tissue and the caudal lobe of the rhesus monkey. Dog prostate contains much less enzyme than human tissue. Cat, guinea pig, rabbit, and rat prostates contain little (SO). Synthesis... 

Fig. 5. Action of different concentrations of NaF on phenol (jumole) liberated by human prostatic phosphatase in the presence of different amounts of phenyl phosphate. From Vescia and Chance (4D-...

Appleyard (64) noted that addition of ethanol to incubation mixtures of sodium phenolphthalein diphosphate with prostatic extract increased the rate of free phenolphthalein formation. Phosphate ion failed to show a comparable increase, and this discrepancy was attributed to transphosphorylation. Phosphoryl transfer may be effected by prostatic phosphatase to acceptors other than solvent (65-67). Nigam and Fishman (25) studied phosphoryl transfer under conditions of 60-80% transfer to an acceptor. In the case of 1,4-butanediol, the optimal concentration was 0.8 M. In this experiment, water molecules outnumbered acceptor molecules by 55/0.8 or 70-fold. In spite of this, transfer far exceeded hydrolysis. Phosphoryl transfer to aliphatic alcohols can be easily measured when phosphates are used as donor compounds. The difference between alcohol formation from the substrate and phosphate ion production is a measure of the transfer reaction. Table IX (25) shows that four different substrates can transfer phosphoryl to butanediol with high efficiency. Table X (25) shows that aliphatic alcohols are good acceptors... 

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