Phosphomonoesterase, inhibition

Acid phosphomonoesterase (EC 3.1.3.2). Milk contains an acid phosphatase which has a pH optimum at 4.0 and is very heat stable (LTLT pasteurization causes only 10-20% inactivation and 30 min at 88°C is required for full inactivation). Denaturation of acid phosphatase under UHT conditions follows first-order kinetics. When heated in milk at pH 6.7, the enzyme retains significant activity following HTST pasteurization but does not survive in-bottle sterilization or UHT treatment. The enzyme is not activated by Mg2+ (as is alkaline phosphatase), but it is slightly activated by Mn2+ and is very effectively inhibited by fluoride. The level of acid phosphatase activity in milk is only about 2% that of alkaline phosphatase activity reaches a sharp maximum 5-6 days post-partum, then decreases and remains at a low level to the end of lactation. 

Diaz-Maurino, T. and Nieto, M. 1976. Milk fat globule membranes. Inhibition by sucrose of the alkaline phosphomonoesterase. Biochim. Biophys. Acta 448, 234-244. Diaz-Maurifio, T. and Nieto, M. 1977. Milk fat globule membranes Chemical composition and phosphoesterase activities during lactation. J. Dairy Res. 44, 483-493. Dowben, R. M., Brunner, J. R. and Philpott, D. E. 1967. Studies on milk fat globule membranes. Biochim. Biophys. Acta 135, 1-10. 

York, J.D., Ponder, J.W., and Majerus, P.W., 1995, Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. Proc. Natl. Acad. Sci. U.S.A. 92 5149-5153. 

In rabbit iris sphincter smooth muscle microsomal fraction, there are phosphomonoesterases that degrade IP3 to IP2, IP2 to IP, and IP to free myo-inositol and Pj (Abdel-Latif, 1986). The IP3 phosphatase has been shown to specifically remove the 5-phosphate from IP3 and from cyclic IP3 to produce IP2 and cyclic IP2, respectively. The polyphosphoinositide phosphatase has also been reported to dephosphorylate inositol tetrakisphophate (IP4) to IP3. These enzyme activities are both cytosolic and membranous, dependent on Mg2+, and not inhibited by Li+. The IP3 5-phospha-tase was studied in the microsomal fraction of bovine iris sphincter muscle (Wang et al., 1994). It hydrolyzed IP3 to I(1,4)P2 with an apparent of 28 (xM Mg2+ was required for its activity, Ca + (> 0.5 (xM) was inhibitory, and Li+ or phosphorylation of the microsomal fraction with cAMP-dependent protein kinase or protein kinase C (PKC) had no effect on the activity of the enzyme. 

From these data it appears that through the action of specific inositol phosphatases both IP3 and IP4 are sequentially dephosphorylated to free inositol (cf. Fig. 2). The dephosphorylation of IP3 requires Mg2+ and physiological concentrations of Ca +. The inositol phosphate phosphomonoesterase is inhibited by Li+, but the IP3 5 -phosphomonoesterase is not inhibited (Carsten and Miller, 1990). Interestingly, soluble and particulate extracts from porcine skeletal muscle also metabolize IP3 and IP4 to inositol in a stepwise fashion (Foster et al., 1994). Apparently, smooth and skeletal muscles have the same set of inositol polyphosphate phosphatases, although their functional role in skeletal muscle is not known. 

This enzyme is an alkaline phosphomonoesterase that catalyzes the hydrolysis of nucleoside 5 -monophosphates (e.g., adenosine-5 -monophosphate and inosine-5 -monophosphate). It appears to be distributed widely in the body tissues and to be mainly a membrane-bound enzyme, but it is also found in the cytoplasm, lysosomes, and other subcellular organelles. In the liver, the enzyme is located on the bile canicular membrane and on other cells, including the sinusoidal cells, leading to its use for the detection of hepatobiliary injury (Goldberg 1973 Dooley and Racich 1980 Carakostas, Power, and Banerjee 1990 Sunderman 1990). The enzyme measurement has largely been discarded in clinical medicine however, more recently, the 5 -NT enzymes have been implicated in the inhibition of antiviral nucleosides, so interest may be revived (Hunsucker, Mitchell, and Spychala 2005). 

Durrieu et al. (2003) investigated the effects of chromium, nickel, copper, zinc, cadmium, mercury and lead on surface phosphomonoesterase activity of Chlorella vulgaris. In all cases decreased markedly with increasing metal concentration, with values only 5% of the control at 1.26 mg/1 cadmium or mercury. The sequence of toxicity towards the inhibition of was approximately the same for each concentration studied. The situation for K... 

The relatively recalcitrant dissolved poly-phenolic compounds resulting from breakdown of higher plants (fulvic and humic acids) complex with many bacterial and algal enzymes, but particularly phosphatases (Wetzel, 1992). The formation of such complexes inactivates phosphomonoesterase (Boavida and Wetzel, 1998), which is inhibited both competitively and non-competitively (Wetzel, 1992). Phosphorus-limited cells therefore need to expend more energy on phosphatase synthesis, and enhanced phosphomonoesterase activity has been reported for waters with increased humic materials (Stewart and Wetzel, 1992b). Wetzel (1992) pointed out these results with frequent observations (e.g. Jones, 1990) that the primary production in humic-rich waters is consistently lower than in clear waters with comparable loadings and light availability. 

Phosphomonoesterase activity is inhibited competitively by phosphate, one of the products of hydrolysis. Such inhibition has been investigated with respect to phosphate concentrations in the external environment,... 

Cathepsin C is inhibited by excess substrate. Numerous examples of product inhibition of enzyme action are known. Phosphate inhibition of acid phosphomonoesterase activity is well documented (Chersi et al.. 

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