Monooxygenase activity

Squalene monooxygenase, an enzyme bound to the endoplasmic reticulum, converts squalene to squalene-2,3-epoxide (Figure 25.35). This reaction employs FAD and NADPH as coenzymes and requires Og as well as a cytosolic protein called soluble protein activator. A second ER membrane enzyme, 2,3-oxidosqualene lanosterol cyclase, catalyzes the second reaction, which involves a succession of 1,2 shifts of hydride ions and methyl groups. 

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

Although a maj ority of research activities were dedicated to cycloketone converting BVMOs, the recently discovered novel MOs also enable stereoselective oxidation of noncyclic ketones to esters. An aliphatic open-chain monooxygenase (AOCMO) from Pseudomonas Jluorescens DSM 50106 displays stereoselective biooxidation of terminal acyl-groups in proximity to hydroxyls (Scheme 9.23). The biooxidation gives acetic... 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

There is increasing evidence that microsomal monooxygenases with cytochrome P450 as their active center have a dominant role in the detoxication of the great... 

FIGURE 2.8 Monooxygenase activities of mammals, birds, and fish, (a) Mammals and birds, (b) Mammals, birds, and fish. Activities are of hepatic microsomal monooxygenases to a range of substrates expressed in relation to body weight. Each point represents one species (males and females are sometimes entered separately) (from Walker et al. 2000). 

Emphasis is given to the critical role of metabolism, both detoxication and activation, in determining toxicity. The principal enzymes involved are described, including monooxygenases, esterases, epoxide hydrolases, glutathione-5 -transferases, and glucuronyl transferases. Attention is given to the influence of enzyme induction and enzyme inhibition on toxicity. 

TBTs also cause inhibition of the P450 of monooxygenases. In fish and in the common whelk, TBT causes conversion of P450s to the inactive P420 form (Pent et al. 1998, Mensink 1997). In fish, inactivation was also found with TPT, and was related to the inhibition of ethoxy resorufin deethylase activity (EROD) activity. In these studies, organotin compounds were found both as substrates and deactivators of the hemeprotein (cf. the interaction of organophosphates with B-type esterases). 

A nnmber of other examples are known in which genetically based resistance was dne to enhanced detoxication of OPs. These include malathion resistance in some stored product pests owing to high carboxylesterase activity, and resistance of strains of the housefly to diazinon due to detoxication by specific forms of a glutathione-S-transferase and monooxygenase (Brooks 1972). 

Walker, C.H. (1978). Species differences in microsomal monooxygenase activities and their relationship to biological half lives. Drug Metabolism Reviews 7(2), 295-323. 

Webb, R.E., Randolph, W.C., and Horsfall, E. Jr. (1972). Hepatic benzo(a)pyrene monooxygenase activity in endrin susceptible and resistant pine mice. Life Science 11 Part 2, 477 84. 

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