Oxidase activity, mixed function

After removal of free Emulgen 913 from partially purified hepatic cytochrome P-448 of DBA-treated male skates an active mixed-function oxidase system was reconstituted by preincubating the cytochrome with purified rabbit hepatic NADPH-cytochrome o... 

The answer is 2 [11 B 2]. Young animals have fewer or less active mixed function oxidases (MFCs) than adults. In addition, fat depots and the blood-brain barrier are poorly developed In neonates, generally increasing their susceptibility to toxicants, xual maturity has more effect on die biotransformation capabiliti of males than fmales, and males, with high testosterone levels, are more likely to have highly active biotransformation enzymes. 

The second type of enzyme was, therefore, referred to as a mixed function oxygenase or mixed function oxidase because, as will be described later, these enzymes are bifunctional, carrying out oxidase activity on one site and oxygenase activity on the other. Recently the term hydroxylase has been preferred to mixed function oxidase or mixed function oxygenase, presumably because the former is more concise and convenient (Massart and Vercauteren, 1959). 

Structural analogy with sphingosine prompts a predicted metabolic pathway for FB j. In Fig. 5 it is predicted that FB) may be (i) acylated by ceramide synthetase with or without removal of the side chains by carboxylesterase action and (ii) de-aminated by either monoamine oxidases or mixed function oxidases with or without esterase action to yield metabolites that would be expected to be inactive, since a free amino group appears to be required for activity. However, none of the metabolites predicted in Fig. 5 are likely to be highly active. 

FIGURE 18.37 (a) Vitamin D3 (cholecalciferol) is produced in the skin by the action of sunlight on 7-dehydrocholesterol. The successive action of mixed-function oxidases in the liver and kidney produces 1,25-dihydroxyvitamin D3, the active form of vitamin D. 

FIGURE 25.42 The mixed-function oxidase activity of 7ff-hydroxylase. 

Acetaminophen, which depletes hepatic glutathione, does not potentiate the toxicity of methyl parathion in mice. A possible mechanism of action may be competition between acetaminophen and methyl parathion for mixed function oxidases and subsequent prevention of activation of methyl parathion to methyl paraoxon (Costa and Murphy 1984). Diethyl maleate, an agent that depletes cytosolic glutathione and is not an enzyme inducer, potentiates toxicity of methyl parathion in mice (Mirer et al. 1977). 

Hewitt LM, JH Carey, KR Munkittrick, JL Parrott, KR Solomon, MR Servos (1998) Identification of chloro-nitro-trifluoromethyl-substituted dibenzo-/ -dioxins in lampricide formulations of 3-trifluoromethyl-4-nitrophenol assessment to induce mixed function oxidase activity. Environ Toxicol Chem 17 941-950. 

NS (acute) (general population) Hepatic Decreased mixed function oxidase activity NS (children) Alvares et al. 1975 Saenger et al. 1984... 

Acrylonitrile alone has little tendency to produce duodenal ulcers in animals, but pretreatment with phenobarbital or Aroclor results in a marked increase in the incidence of such ulcers (Szabo et al. 1983, 1984). Although the mechanism of the ulcerogenic effect is not obvious, these data indicate that agents which enhanced mixed-function oxidase activity may also increase the toxicity of acrylonitrile. 

Figure 5. Metabolic activation pathways of BA. MFO abbreviates for the cytochrome P-450-containing mixed-function oxidases. The absolute configurations of the metabolites are as shown.

Oxidation is intimately linked to the activation of polycyclic aromatic hydrocarbons (PAH) to carcinogens (1-3). Oxidation of PAH in animals and man is enzyme-catalyzed and is a response to the introduction of foreign compounds into the cellular environment. The most intensively studied enzyme of PAH oxidation is cytochrome P-450, which is a mixed-function oxidase that receives its electrons from NADPH via a one or two component electron transport chain (10. Some forms of this enzyme play a major role in systemic metabolism of PAH (4 ). However, there are numerous examples of carcinogens that require metabolic activation, including PAH, that induce cancer in tissues with low mixed-function oxidase activity ( 5). In order to comprehensively evaluate the metabolic activation of PAH, one must consider all cellular pathways for their oxidative activation. 

L The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (Hz) blockers. 

Nickel concentrations in livers of birds fed sludge- 3 grown wheat were significantly elevated in males (210 pg Ni/kg DW vs. 130 in controls) and females (120 vs. 80 pg Ni/kg DW) mixed function oxidase activities were elevated in livers of both sexes when compared to controls... 

Arinc, E. and A. Sen. 1994. Effects of in vivo benzo[a]pyrene treatment on liver microsomal mixed-function oxidase activities of gilthead seabream (Sparus aurata). Comp. Biochem. Physiol. 107C 405-414. 

Gerhart, E.H. and R.M. Carlson. 1978. Hepatic mixed-function oxidase activity in rainbow trout exposed to several polycyclic aromatic compounds. Environ. Res. 17 284-295. 

The assay can be performed using mutagenic substances that react directly with DNA or, where metabolic activation is necessary, with pre-mutagen in the presence of rat liver homogenate that is enriched in mixed function oxidases (termed S9). Metabolic oxidation (if that is what is required) results in ultimate or penultimate mutagenic forms, which act as electrophiles towards S. typhimurium. 

Robertson P, White EL, Bus JS. 1989. Effects of methyl ethyl ketone pretreatment on hepatic mixed-function oxidase activity and on in vivo metabolism of -hexane. Xenobiotica 19(7) 721-729. 

Knights KM, Gourlay GK, Cousins MJ. Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. Biochem Pharmacol 1987 36(6) 897-906. 

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