Phosphoric triester hydrolases

Phosphatases of documented or potential interest in the context of this book include phosphoric monoester hydrolases (EC 3.1.3), phosphoric diester hydrolases (EC 3.1.4), and phosphoric triester hydrolases (EC 3.1.8). 

Phosphatases are numerous and important enzymes (see also Chapt. 2). They are classified as phosphoric monoester hydrolases (phosphatases, EC 3.1.3), phosphoric diester hydrolases (phosphodiesterases, EC 3.1.4), triphosphoric monoester hydrolases (EC 3.1.5), diphosphoric monoester hydrolases (pyrophosphatases, EC 3.1.7), and phosphoric triester hydrolases (EC 3.1.8) [21] [63]. Most of these enzymes have a narrow substrate specificity restricted to endogenous compounds. However, some of these enzymes are active toward xenobiotic organophosphorus compounds, e.g., alkaline phosphatase (EC 3.1.3.1), acid phosphatase (EC 3.1.3.2), aryldialkylphosphatase (para-oxonase (PON1), EC 3.1.8.1) and diisopropyl-fluorophosphatase (tabunase, somanase, EC 3.1.8.2) [64 - 70]. However, such a classification is far from definitive and will evolve with further biochemical findings. Thus, a good correlation has been found in human blood samples between somanase and sarinase activities on the one hand, and paraoxonase (PON1) type Q isozyme concentrations on the other [71]. 

The inactivation and detoxification of paraoxon and congeners are catalyzed by the so-called A-esterases, which, as discussed, comprise aryleste-rase (sometimes still called paraoxonase, EC 3.1.1.2) and phosphoric triester hydrolases (phosphotriesterases, EC 3.1.8) subdivided into aryldialkylphos-phatase (organophosphate hydrolase, paraoxonase, EC 3.1.8.1) and organophosphorus acid anhydrolases (EC 3.1.8.2 see Sect. 9.3.7) [65][69][106-108], These activities, which occur mostly in the mammalian liver and... 

In a classification from 1992 (International Union of Biochemistry, 1992) hydrolases of OP were described as a special entity as phosphoric triester hydrolases which comprise three groups of enzymes phosphoric monoester hydrolases (EC 3.1.3), phosphoric diester hydrolases (EC 3.1.4), and phosphoric triester hydrolases (phosphotriesterases) (EC 3.1.8). Phosphoric triester hydrolases are further divided in two similar subgroups aryldialkylphos-phatases (EC 3.1.8.1) and diisopropylfluorophosphatases (EC 3.1.8.2). 

EC 3.1.8 Phosphoric triester hydrolases EC 3.1.8.1 Paraoxonase (PON) PONl, PON2, PON3 EC 3.1.8.2 Diisopropyl-fluorophosphatase... 

Methods have been published that allow the classification of two types of esterases, the carboxylic ester hydrolases (CEHs) and the phosphoric triester hydrolases (PTEHs) (Anspaugh and Roe, 2004). The CEHs contain the B-esterases, which are inhibited by organophosphates. B-esierases include many other esterases, such as CarbE, acetylcholinesterase (AChE), cholinesterases (ChE), aryleslerases, sterol esterases, insect juvenile hormone esterases, aixl others. The determination of A-esterases uses a protocol for the detection of PTEHs. The PTEH assay allows for the identification of two subclasses of esterases, the A-esterase (known as aiyldialkylphos-phatase) and ditsopropyl fluorophosphatase. Both these enzymes metabolize OP compounds. 

DFP is a phosphoric triester consequently, it is not subjected to bioactivation through desulfuration, as in the case of thiophosphates such as chlorpyrifos, mala-thion, and other OP compoimds used as insecticides. DFP can be enzymatically hydrolyzed by the enzymes called phosphotriesterases or phosphoric triester hydrolases according to the nomenclature of the International Union of Biochemistry and Molecular Biology (Table 57.3). The hydrolysis of DFP releases the fluoride ion and the acidic moiety of DFP, the DIP. This hydrolysis must be considered a detoxication reaction (Sogorb and Vilanova, 2010). 

Classified in 1992 (International Union of Biochemistry, 1992), hydrolases of OP were described as a special entity called "phosphoric triester hydrolases," which comprise... 

In the literature published during the past 30 years, tire term PONl apparently covers both phosphoric triester hydrolases. In further text, to avoid possible confusion, tire term A-esterase will be generally used for enz3unes hydrolyzing OPs and with otirer terms (such as PONl, paraoxonase, etc.) as they appear in original references. 

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