Phosphohydrolase

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

SIP is formed from sphingosine by sphingosine kinases (SphKs). Degradation of SIP occurs either reversibly by lipid phosphate phosphohydrolases (LPPs) and SIP phosphatases (SPPs), or irreversibly by SIP lyase (SPL) (Fig. 1). The localization of SIP production is highly important since SIP plays a role both as extracellular mediator and as intracellular... 

A 1,5-hour inhalation exposure of mixed breed rabbits to airborne concentrations of 72 ppm of hydrogen sulfide resulted in ventricular repolarization, while a 5-day, 0.5-hour/day exposure to this concentration resulted in cardiac arrhythmia (Kosmider et al. 1967). Histochemical staining of the myocardial cells revealed a reduction in adenosine tri-phosphate (ATP) phosphohydrolase and NADPH2 oxidoreductase (Kosmider et al. 1967). Cardiac arrhythmia, suggestive of a stimulus transmission disorder, was... 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

AP isoenzymes can cleave associated phosphomonoester groups from a wide variety of substrates. The exact biological function of these enzymes is not well understood. They can behave in vivo in their classic phosphohydrolase role at alkaline pH, but at neutral pH AP isoenzymes can act as phosphotransferases. In this sense, suitable phosphate acceptor molecules can be utilized in solution to increase the reaction rates of AP on selected substrates. Typical phosphate acceptor additives include diethanolamine, Tris, and 2-amino-2-methyl-lpropanol. The presence of these additives in substrate buffers can dramatically increase the sensitivity of AP ELISA determinations, even when the substrate reaction is done in alkaline conditions. 

McGill and Cole (1981) suggested that the concentration of available P in the soil depended on biochemical mineralization, i.e., mineralization by extracellular enzymes, which does not provide energy to organisms and depends on the amount of enzymes present. This is controlled by the need for P. Thus, organic P input into the soil only influences the size of the total pool, while plants, microbes, and mycorrhiza can make P available by releasing phosphatases and phosphohydrolases into the soil. Phosphatase excretion has been used as an indicator of the P status of plants (Johnson et al. 1999 Phoenix et al. 2004). 

Pittner, R.A., Fears, R. and Brindley, D.N. (1985). Effects of glucocorticoids and insulin on activities of phosphatidate phosphohydrolase, tyrosine aminotransferase and glycerol kinase in isolated rat hepatocytes in relation to the control of triacyglycerol synthesis and gluconeogenesis. Biochem. J. 225 455—462. 

The activity of PLD on phosphatidylcholine generates phosphatidic acid, and this may be further metabolised by the enzyme phosphatidate phospho-hydrolase to form DAG (Fig. 6.19). Furthermore, the activity of DAG kinase can convert the DAG (generated either from phosphatidic acid or from the activity of PLC) back into phosphatidic acid. Both phosphatidic acid and DAG have functions as second messengers thus the activities of PLD, phosphatidate phosphohydrolase and DAG kinase all play important roles in the generation of these intracellular signalling molecules. 

The enzyme phosphatidate phosphohydrolase can be inhibited by propranolol, although this inhibitor is not completely specific. Thus, propranolol treatment of neutrophils results in the increased formation of phosphati-dic acid and the decreased formation of DAG. There is increasing evidence... 

Billah, M. M., Eckel, S., Mullmann, T. J., Egan, R. W., Siegel, M. I. (1989). Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction. J. Biol. Chem. 264, 17069-77. 

Aravind, L., and Koonin, E. V. (1998a). The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Trends Biochem. Sd. 23, 469—472. 

The enthalpies of hydrolysis of glycoside cyclic phosphodiesters have been measured42 by flow microcalorimetry, using a phosphohydrolase from Enterobacter aerogenesiz as catalyst. This phosphohydrolase can hydrolyse a wide variety of phosphodiesters, which enables the enthalpies of hydrolysis of glycoside cyclic phosphodiesters to be compared with those of acyclic and monocyclic phosphodiesters. It was found42 that the phosphohydrolase cleaves the 3 - and 5 -ester bonds with similar enthalpies, which are less negative (—11.1 0.2 kcal mol-1) than the value (-13.2 0.4 kcal mol-1) that had been reported previously.44... 

Jones, 1990 Nishizuka 1992 and 1995). The second, more sustained inaease in DAG comes from the hydrolysis of PC by PC-specific PLC (direct-route), or indirectly via the sequmtial activation of phosphohpase D (PLD) and phosphatidic acid phosphohydrolase (PAP) to generate PA and DAG, respectively. The second phase of DAG production proceeds without an elevation in the concentration of intracellular and might be related to the activation of Ca -independent protein kinase C isoforms (Wakelam, 1998). 

Brindley, D.N. and Waggoner, D.W., 1998, Mammalian Upid phosphate phosphohydrolases,... 

Bergstrom, J., Kurtz, M.B. and Spiegel, S., 2000, Molecular cloning and characterization of a novel lipid phosphohydrolase that degrades sphingosine 1-phosphate and induces cell death, Proc. Nat. Acad. Sci U.S.A. 97 7859-7864. 

Mullmann, T.J., Siegel, M.L, Egan, R.W. and Billah, M.M., 1991, Sphingosine inhibits phosphatidate phosphohydrolase in human neutrophils by a protein kinase C-independent mechanism, J. Biol. Chem. 266 2013-2016. 

This enzyme [EC 3.1.3.26], also known as phytase, phy-tate 6-phosphatase, and myo-inositol-hexaphosphate 6-phosphohydrolase, catalyzes the hydrolysis of myoinositol hexakisphosphate to produce 1-myo-inositol... 

PHOSPHATIDYLGLYCEROL PHOSPHATE PHOSPHOHYDROLASE PHOSPHOENOLPYRUVATE CARBOXYKI-NASE (PYROPHOSPHATE)... 

Grivell, A.R. Jackson, J.F. Thymidine phosphotransferase and nucleotide phosphohydrolase of the fern Asplenium nidus. General properties and inhibition by adenosine 3 5-cyclic monophosphate. Biochem. J., 155, 571-581 (1976)... 

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