Oxygenases mixed

Cytochrome P450 (CYP) Cytochrome P450 isozymes Cytochrome P450 mono-oxygenases Mixed function oxidases... 

FIGURE 4.2 The catalytic cycle of the cytochrome(s) P-450 mono-oxygenase (mixed function oxidase) system. Adapted from Tukey and Johnson (1990) in Principles of Drug Action, edited by W.B. Pratt and P. Taylor (New York ... 

Cytochrome P450 (CYP) mono-oxygenases, also called mixed function oxidases, are versatile hemoprotein enzymes that catalyze the cleavage of molecular oxygen to incoiporate one oxygen atom into a substrate molecule and one atom into water [1]. The general stoichiometry of the reaction is as follows (S-H, substrate) ... 

Tyrosine. Phenylalanine hydroxylase converts phenylalanine to tyrosine (Figure 28-10). Provided that the diet contains adequate nutritionally essential phenylalanine, tyrosine is nutritionally nonessential. But since the reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Catalysis by this mixed-function oxygenase incorporates one atom of O2 into phenylalanine and reduces the other atom to water. Reducing power, provided as tetrahydrobiopterin, derives ultimately from NADPH. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

Kirchin MA, A Wiseman, DR Livingstone (1992) Seasonal and sex variation in the mixed-function oxygenase system of digestive gland microsomes of the common mussel, My til us edulis L. Comp Biochem Physiol lOlC 81-91. 

Livingstone DR, SV Farrar (1984) Tissue and subcellular distribution of enzyme activities of mixed-function oxygenase and benzo[a]pyrene metabolism in the common mussel Mytilis edulis L. Sci Tot Environ 39 209-235. 

Laboratory trials during lampricide application (0.5-5.8 mg/L, 24-h exposure) with rainbow trout confirmed that field formulations of lampricides induce hepatic mixed function oxygenase enzymes activity. Mixed function oxygenase induction was associated with the 3-trifluoromethyl-4-nitrophenol formulation, and not the 2, 5-dichloroU -nitrosalicylanilidc (Bayer 73) component of the field application. Bioassays were successfully confirmed with HPLC [78]. 

FIGURE 13.1 An EPR-monitored redox titration of two [2Fe-2S] clusters. A 2Fe cluster in a ferredoxin (E° = -170 mV) and one in an oxygenase enzyme (E° = -20 mV) from Pseudomonas maltophilia were each titrated with dithionite in the presence of a mediator mix. Each point is the EPR amplitude from an individual sample drawn at the indicated solution ii-value. The fit is based on Equation 13.12. (Data from Chakraborty et al. 2005.)... 

Tyle, H., M. Egsmose, and N. Harrit. 1991. Mixed-function oxygenase in juvenile rainbow trout exposed to hexachlorobenzene or 3,3, 4,4 -tetrachlorobiphenyl. Comp. Biochem. Physiol. 100C 161-164. 

Trust, K.A., A. Fairbrother, andM.J. Hooper. 1994. Effects of 7,12-dimethylbenz[a]anthracene on immune function and mixed-function oxygenase activity in the European starling. Environ, Toxicol. Chem. 13 821-830. 

Choice of Tissue. The next choice is that of source tissue. Preparations derived from liver are the most useful, as this tissue is a rich source of mixed-function oxygenases capable of converting procarcinogens to genetically active electrophiles. However,... 

Both mirex and chlordecone are microsomal enzyme inducers, and as such enhance the metabolism of compounds oxidized or reduced by the mixed function oxygenase system. For... 

Klingensmith JS, Mehendale HM. 1983a. Destruction of hepatic mixed-function oxygenase parameters by CC14 in rats following acute treatment with chlordecone, mirex, and phenobarbital. Life Sci 33(23) 2339-2348. 

Parrott, J.L. and Tillitt, D.E. 1997,The use of Semipermeable Membrane Devices (SPMDs) to Concentrate Inducers of Fish Hepatic Mixed Function Oxygenase (MFO). In Ecotoxicology Responses, Biomarkers, and Risk Assessment. An OECD Workshop Zelikoff, J.T., Ed. SOS Publications Pair Haven, NJ. pp. 185—196. 

Chaturvedi et al. (1991) studied the effects of mixtures of parathion, toxaphene, and/or 2,4-D on the hepatic mixed-function oxygenase in ICR male mice. They found that a 7-day toxaphene pretreatment enhanced the hepatic biotransformation of parathion and its metabohte paraoxon, both in the presence and absence of NADP. However, in the absence of NADP the enhancement was minor. The authors suggested that toxaphene induced the metabohc pathways of parathion and paraoxon involving the mixed-function oxygenase and that paraoxonase is not involved in the... 

Most phase one reactions are catalyzed by the drug-metabolizing enzymes (mixed function oxidases, oxygenases) located in the endoplasmic reticulum of liver and, to a lesser extent, in intestine, kidney, and lung. These enzymes have been the subject of intensive research (G7, G8, LI). 

Since the formation of the ethyleniminium ion is crucial for the cytotoxic activity of the nitrogen mustards, it is not surprising that stable ethylenimine derivatives have antitumor activity. Thiophospho-ramide or thiotepa is the best known compound of this type that has been used clinically. Both thiotepa and its primary metabolite, triethylenephos-phoramide (TEPA), to which it is rapidly converted by hepatic mixed-function oxygenases form crosslinks with DNA. It is mainly used as an intravesicu-lar agent in bladder cancer. Thiotepa produces little toxicity other than myelosuppression. 

FAO43 Sambaiah, K., and K. Srinivasan. In- FA055 fluence of spices and spice principles on hepatic mixed function oxygenase system in rats. Indian J Biochem Biophys 1989 26(4) 254-258. FA056... 

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