Bone, acid phosphatase

Product inhibition studies on bovine cortical bone acid phosphatase indicate that its reaction with p-nitrophenyl phosphate involves a two-step hydrolytic transfer mechanism (pseudo Uni Bi), with p-nitrophenyl and phosphate as the first and second products released, respectively Moreover, bone phosphatase was inhibited by transition state analogs of phosphate, suggesting formation of a phosphoryl-enzyme intermediate in the reaction. The possibility exists that most, if not all, add phosphatases catalyze their reaction by this two-step transfer mechanism and NMR results of Mn(III) Kintoki phosphatase, which show that the catalytic mechanism involves a transition state displacement and P-O cleavage, also support this idea ... 

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. 

The substrate phenyl phosphate, which is hydrolyzed by the serum acid phosphatases originating from many tissues, has been used in most of the published studies. Total serum acid phenylphos-phatase is elevated in diseases of the liver, disease of bone such as Paget s disease, and several blood dyscrasias, especially those involving platelets (99>100). 

Kim MS, Day CJ, Selinger Cl, Magno CL, Stephens SR, Morrison NA. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATcl, and calcitonin receptor-positive but require receptor activator of NFkap-paB ligand for bone resorption. J Biol Chem 2006 281(2) 1274-1285. 

Phosphates of pharmaceutical interest are often monoesters (Sect. 9.3), and the enzymes that are able to hydrolyze them include alkaline and acid phosphatases. Alkaline phosphatase (alkaline phosphomonoesterase, EC 3.1.3.1) is a nonspecific esterase of phosphoric monoesters with an optimal pH for catalysis of ca. 8 [140], In the presence of a phosphate acceptor such as 2-aminoethanol, the enzyme also catalyzes a transphosphorylation reaction involving transfer of the phosphoryl group to the alcohol. Alkaline phosphatase is bound extracellularly to membranes and is widely distributed, in particular in the pancreas, liver, bile, placenta, and osteoplasts. Its specific functions in mammals remain poorly understood, but it seems to play an important role in modulation by osteoplasts of bone mineralization. 

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]. 

Hayman, A.R., and Cox, T.M. (2003) Tartrate Resistant Acid Phosphatase Knockout Mice. Journal of Bone and Mineral Research 18,1905-1907. 

K.H. Lau, T.K. Freeman, D.J. Baylink, A proposed mechanism of the mitogenic action of fluoride on bone cells. Inhibition of the activity of an osteoblastic acid phosphatase, Metabolism 38 (1989) 858-868. 

Bone contains at least two different acid phosphatases and the more abundant enzyme may function as a pyrophosphate. The physiological substrate for the latter enzyme may be pyrophosphate or another oligophosphate ester. The first enzyme may utilize only monophosphate esters. 

The changes in calvarial phosphatase activities observed in animals treated with 25-(OH)D3 are totally different from those obtained with either 1.25-(OH)2D3 or 24.25—(OH)2D3. This fact indicates that physiological doses of 25-(OH)D3 may have an effect on cellular activity, independent of the conversion of this metabolite into these dihydroxyderivatives. The various effects of these vitamin D3 metabolites cannot be correlated with changes in serum calcium and/or phosphate concentrations. Among those factors other than serum calcium and phosphate concentrations that may be involved in the mechanism of action of vitamin D3 metabolites on bone phosphatase activities, the parathyroid hormone is of importance. This hormone is known to be a potent activator of bone phosphatases223,224,228. Parathormone increases the content of alkaline, neutral and acid phosphatases in mouse calvaria in vitro. Calcitonin does not prevent the increase of those enzymes while dichloromethylene diphosphonate causes a decrease in acid phosphatase and pyrophosphatase226. ... 

Toverud, S. U., Hammarstrom, L. E., Kristoffersen, U. M. Quantitative studies on acid phosphatase in developing rat bones and teeth during hypervitaminosis D. Arch, oral Biol. 20, 175 (1975)... 

Anderson, T. R., Toverud, S. U. Chromatographic separation of two acid phosphatases from rat bone. Calc. Tiss. Res. 24, 187 (1977)... 

In 1924, Martland et al. (1) reported on phosphatase activity in red blood cells. Roche later differentiated between the phosphatase of the red cells with pH optimum 6.0-6.2 and the phosphatase from white cells with optimum 8.8-9.0. Roche also showed that a-glycerophosphate was split more rapidly than -glycerophosphate by red cell extracts while the reverse was true of acid phosphatase activity in plasma (2). While studying the source of acid phosphatase activity in male urine, Kutscher and Wolberg discovered the very high activity of acid phosphatase in human prostate (3). This tissue was shown by Woodard to have one-thousand times the activity of extracts from bone, liver, and kidney (3a). Igarashi and Hollander crystallized the acid phosphatase of rat liver and showed that under certain conditions allosteric control of the activity could be demonstrated (4). 

Bone contains two distinct enzymes, acid and alkaline phosphatases, which are associated with osteoclasts and osteoblasts, respectively (118). Further study of acid phosphatase and bone should be rewarding. Many... 

A number of purple acid phosphatases821 have been isolated from animal sources, including bovine spleen, rat bone and the enamel organ of rat molars. Other phosphatases may belong to this class but the identification is not yet certain. Purple acid phosphatase from the sweet potato, as noted in Section 62.1.3.6.1, contains manganese. 

Blood Alkaline phosphatase (bone-specific) Osteocalcin Procollagen type I carboxy-terminal propeptide (PICP) Procollagen type I amino-terminal propeptide (PINP) Procollagen type III amino-terminal propeptide (PIIINP) Blood Acid phosphatase (acid-resistant) Type I collagen carboxy-terminal telopeptide (ICTP) Urine Calcium Hydroxyproline Cross-linked peptides (pyridinium and deoxypyridinoline)... 

Halleen, J.M., Raisanen, S., Salo, J.J., Reddy, S.V., Roodman, G.D., Hentunen, T.A., Lehenkari, P.P., Kaija, H., Vihko, P., and Vaananen, H.K. 1999. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase. J. Biol. Chem. 274, 22907-22910. 

Activity of the cells participating in bone remodeling. Usually it is the activity of the specific enzymes characteristic for the osteoblasts (especially alkaline phosphatase and its bone isoenzyme) or the osteoclasts, respectively (acid phosphatase or its bone isoenzyme)... 

Tartrate-Resistant Acid Phosphatase, Marker of Bone Resorption (TRACP, EC.3.1.3.2 5-TRACP)... 

HI. Halleen, J. M., Karp, M., Viloma, S., Laaksonen, P., Heilman, J., et al., Two-site immunoassays for osteoclastic tartrate-resistant acid phosphatase based on characterization of six monoclonal antibodies. J. Bone Miner. Res. 14,464-469 (1999). 

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