Phosphatases of bone

Lieberherr, M., Vreven, J., Vaes, G. The acid and alkaline phosphatases, inorganic pyrophosphatases and phosphoprotein phosphatase of bone. I. Characterization and assay. Bio-chim. Biophys. Acta 293, 160 (1973)... 

FIGURE 2-21 The pH optima of some enzymes. Pepsin is a digestive enzyme secreted into gastric juice trypsin, a digestive enzyme that acts in the small intestine alkaline phosphatase of bone tissue, a hydrolytic enzyme thought to aid in bone mineralization. 

B29. Bodansky, 0., Are the phosphatases of bone, kidney, intestine and serum identical The use of bile acids in their differentiation. J. Biol. Chem. 118, 341-362 (1937). 

Pa.g et s Disease of Bone. Paget s disease, osteitis deformans, occurs mainly ia people over 40. About twice as many men as women are affected. The disease, caused by faulty utilisation of may be mild and asymptomatic requiring Httle or no treatment. Clinical signs are high alkaline phosphatase and high urine hydroxyproline as weU as abnormal bone stmcture which usually goes unrecognised until discovered accidentally by routine x-ray examination (32). 

Antithyroid drags have several side effects. The most frequent side effects are maculopapular rashes, pruritus, urticaria, fever, arthralgia and swelling of the joints. They occur in 1-5% of patients [1, 2]. Loss of scalp hair, gastrointestinal problems, elevations of bone isoenzyme of alkaline phosphatase and abnormalities of taste and smell are less common. The incidence of all these untoward reactions is similar with MMI and PTU. Side effects of MMI are dose-related, whereas those of PTU are less clearly related to dose [1]. PTU may cause slight transient increases of serum aminotransferase and y-glutamyl transpeptidase concentrations but also severe hq atotoxicity whereas methimazole or carbimazole can be associated with cholestasis. The side... 

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). 

Gao and Yamaguchi, 1999a Yamaguchi and Ma, 2001 Femoral-diaphyseal tissues from elderly female rats cultured for 24 h Daidzein or genistein (lO M, lO M) induced calcium content and alkaline phosphatase (ALP) activity indicating stimulation of bone formation. 

ALP Alkaline phosphatase BM Bone marrow, bowel movement an isoenzyme of... 

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. 

Diagnosed on the basis of unique histological features. Elevated alkaline phosphatase activity. Fish-scale appearance of bone under the microscope... 

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

The most important organic components of bone are collagens (mainly type 1 see p.344) and proteoglycans (see p. 346). These form the extracellular matrix into which the apatite crystals are deposited (biomineralization). Various proteins are involved in this not yet fully understood process of bone formation, including collagens and phosphatases. Alkaline phosphatase is found in osteoblasts and add phosphatase in osteoclasts. Both of these enzymes serve as marker enzymes for bone cells. 

Paget disease of bone For treatment of Paget disease of bone where alkaline phosphatase is at least 2 times the upper limit of normal, or those who are symptomatic or at risk for future complications from their disease (alendronate, risedronate, tiludronate) treatment of symptomatic Paget disease (etidronate) treatment of moderate to severe Paget disease (pamidronate). 

A study in 500 Australian women (aged 40 to 80 years) has shown that higher isoflavone intakes are associated with higher concentrations of bone alkaline phosphatase, a short-term marker of bone formation and turnover. 

The acoustic micrograph in Fig. 1.5(a) came from a 5-week-old preparation. It was fixed in alcohol, and stained for alkaline phosphatase and, with von Kossa stain, for biomineral material. The biomineral material of interest here is hydroxyapatite, the principal crystalline mineral constituent of bone. The ordered structure visible within the matrix is not seen with either the light or electron microscopes. But the acoustic microscope can also work perfectly well with unfixed, unstained specimens. Figure 1.5(b) is an acoustic micrograph of matrix and cells from a 17-year-old male. In addition to the standard ingredients of culture medium, these cells were specifically stimulated with beta-glycerolphosphate and a vitamin C preparation. Because the acoustic... 

Phosphatases. Of particular importance is the observation that enzymes obviously involved in biomineralization processes occur in bone. 

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. ... 

The alkaline phosphatases are found in bacteria, fungi, and higher animals but not in higher plants. In E. coli alkaline phosphatase is concentrated in the peri-plasmic space. In animals it is found in the brush border of kidney cells, in cells of the intestinal mucosa, and in the osteocytes and osteoblasts of bone. It is almost absent from red blood cells, muscle, and other tissues which are not involved extensively in transport of nutrients. 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

At the present time it is not possible to assign a precise function for any alkaline phosphatase. Undoubtedly bone phosphatase is concerned in ossification and two alternative roles have been proposed (1) Precipitation of calcium phosphate is induced by the localized production of high concentrations of Pi owing to phosphatase activity (33) (2) the enzyme permits crystal growth at nucleation sites in the matrix by ensuring the removal and continued absence of PPi which is known to be a crystal poison (60). Other factors must be involved (35) because tissues with high concentrations of alkaline phosphatase (e.g., gut, kidney, and... 

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... 

Glucocorticoids can even cause osteoporosis when they are used for long-term replacement therapy in the Addison s disease, as has been shown by a study of 91 patients who had taken glucocorticoids for a mean of 10.6 years, in whom bone mineral density was reduced by 32% compared with age-matched controls (SEDA-19, 377 198). However, these results contrasted with the results of a Spanish study in patients with Addison s disease, in which no direct relation was found between replacement therapy and either bone density or biochemical markers of bone turnover of calcium metabolism (alkaline phosphatase, osteocalcin, procollagen I type, parathormone, and 1,25-dihydroxycolecalciferol) (SEDA-19, 377 199). 

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