Mammalian paraoxonase

Another family of enzymes that exhibit the same properties are mammalian paraoxonases, whose original activity is hydrolysis of five- and six-membered lactones [104]. 

Aharoni, A. et al. Directed evolution of mammalian paraoxonases PON 1 and PON3 for bacterial expression and catal3dic specialization, Proc. Natl. Acad. Sci. U.S.A., 101, 482, 2004. 

Amitai, G. et al. Enhanced stereoselective hydrolysis of toxic organophosphates hy directly evolved variants of mammalian paraoxonase. FEES J., TTi, 1906, 2006. 

Otto, T.C., Harsch, C.K., Yeung, D.T., et al., 2009. Dramatic differences in organophosphorus hydrolase activity between human and chimeric recombinant mammalian paraoxonase-1 enzymes. Biochemistry 48,10416-10422. 

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... 

Various esterases exist in mammalian tissues, hydrolyzing different types of esters. They have been classified as type A, B, or C on the basis of activity toward phosphate triesters. A-esterases, which include arylesterases, are not inhibited by phosphotriesters and will metabolize them by hydrolysis. Paraoxonase is a type A esterase (an organophosphatase). B-esterases are inhibited by paraoxon and have a serine group in the active site (see chap. 7). Within this group are carboxylesterases, cholinesterases, and arylamidases. C-esterases are also not inhibited by paraoxon, and the preferred substrates are acetyl esters, hence these are acetylesterases. Carboxythioesters are also hydrolyzed by esterases. Other enzymes such as trypsin and chymotrypsin may also hydrolyze certain carboxyl esters. 

Khersonsky, O., Tawfik, D.S. (2006). The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases. J. Biol. Chem. 281 7649-56. 

Amitai, G., Gaidukov, L., Adani, R., Yishay, S., Yacov, G., Kushnir, M., Teitlboim, S., Lindenbaum, M., Bel, P., Khersonsky, O., Tawfik, D.S., Meshulam, H. (2006). Enhanced stereoselective hydrolysis of toxic OPs hy directly evolved variants of mammalian semm paraoxonase. FEBSJ. 273 1906-19. 

Mammalian PON1 (serum paraoxonase) Lipo-lactonase - aliphatic 5-, PON1 Aryl esterase (phenyl 91,92... 

Kaufer, D., Friedman, A., Seidman, S., et al, 1998. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 393, 373-377. Khersonsky, O., Tawfik, D.S., 2006. The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases. J. Biol. Chem. 281, 7649-7656. 

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