Ethoxycoumarin deethylase

Species Aniline hydrolase d-Benzphetamine demethylase 7-Ethoxycoumarin deethylase... 

The MFO system is also known as the aryl hydrocarbon hydroxylase (AHH) or drug-metabolizing system in mammals. In fish, as in mammals, most MFO activity is localized in the liver (2.404 /imoles of B[a]P hydroxylase = AHH) and in minor amounts in kidney (0.026) and heart (0.006) (Pederson etaL, 1974). Many studies have shown the presence of various oxygenases in fish (Bend etal, 1977 Stegeman, 1978). AHH is present in many marine fish species from different habitats and life stories (Payne, 1977). Several fish species including rainbow trout can hydroxylate benzo[a]pyrene and naphthalene. Quantitative data on AHH activity based on B[a]P hydroxylase activity, benzphetamine demethylase activity, 7-ethoxycoumarin deethylase activity, and cytochrome P-450 content in vertebrates, crustaceans, and bivalves are available in the literature (Vandermeulen and Penrose, 1978 Philpot etaL, 1976). Specific enzyme activities derived from single substrate measurements are limited in their application to complex mixtures of petroleum hydrocarbons (Malins, 1977a, b). MFO absence or activity could determine hydrocarbon retention in... 

Whole liver homogenates had increases of 300-fold in 7-ethoxycoumarin O-deethylase and 75-fold in AHH activities between days 5 and 10 LD50 by time of hatch... 

Brunstrom, B. 1986. Activities in chick embryos of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon (benzo[a]pyrene) hydroxylase and their induction by 3,3, 4,4 -tetrachlorobiphenyl in early embryos. Xenobiotica 16 865-872. 

In this study, P-450-related enzyme activities (benzphetamine N-demethylase, 7-ethoxycoumarin O-deethylase) were also measured in liver homogenates (prepared 24 hours after the last treatment) from rats treated orally with MEK for 1-7 days and compared to the activity obtained with phenobarbital treatment (80 mg/kg intraperitoneally for 3 days) (Robertson et al. 1989). Total cytochrome P-450 was also measured. No consistent change was noted in benzphetamine N-demethylase activity as the result of MEK treatment, while 7-ethoxycoumarin O-deethylase was over 3 times higher than controls and comparable to phenobarbital induction. Total P-450 levels were increased to approximately 150-200% of controls with MEK and to 570% of control by phenobarbital. The authors concluded that the potentiating effects of MEK on the neurotoxicity of -hexane appear to arise, at least in part, from the activating effects of MEK on selected microsomal enzymes responsible for -hexane activation. 

An MRL of 3 mg/kg/day has been derived for acute oral exposure to di-M-octylphthalatc. This MRL is based on liver effects observed in rats administered di- -octylphthalate via gavage at a dose of 1,000 mg/kg/day (Lake et al. 1986). The hepatic effects consisted of a statistically significant (p<0.01) 17% increase in relative liver weight and a statistically significant (p<0.05) reduction in enzyme (7-ethoxycoumarin 0-deethylase) activities. The LOAEL was divided by an uncertainty factor of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and... 

Moon, J.Y., Lee D.W., and Park, K.H., Inhibition of 7-ethoxycoumarin O-deethylase activity in rat liver microsomes by naturally occurring flavonoids structure-activity relationships, Xenobio-tica, 28, 117, 1998. 

An assay for ethoxycoumarin O-deethylase is useful in as a part of a battery of tests for cytochrome P450 activities in a variety of tissues. The deethylase activity results in the conversion of 7-ethoxycoumarin to 7-hydroxycoumarin. A postcolumn pH shift allows the product to be detected by fluorescence. 

Chui et al, [96] have reported that PCDE 74 (2,4,4, 5-tetraCDE) induce 7-ethoxycoumarin O-deethylase activities in trout and PCDE 28 (2,4,4-triCDE) and PCDE 74 (2,4,4, 5-tetraCDE) in rats. The effects of PCDEs were studied by administering PCDEs 100 mg kg 1 day 1 to rats and trout for three days. Chui et al. [96] classified PCDE 28 as a phenobarbital (PB)-type inducer and PCDE 74 a mixed-type inducer. Due to the fact that PCDEs cannot adopt planar configuration, it was suggested that PCDEs cannot act as 3-methyl chloranthrene(MC)-type inducers unlike non-orfho-PCBs. PCBs that are not acutely toxic can still induce toxic and biochemical responses and are PB-type inducers of hepatic drug-metabolizing enzymes [79]. 

Phase 1 detoxification enzymes. The response of the mixed-function oxidase system can be measured via several of its components, the most common being cytochrome P450 levels and the activities of ethoxyresorufin O-deethylase (EROD), ethoxycoumarin O-dealkylase (ECOD), aryl hydrocarbon hydroxylase (AHH) and NADPH cytochrome c reductase. 

AHH aryl hydrocarbon hydroxylase ECOD ethoxycoumarin O-deethylase... 

Ito, T., Y. Aoyama, K. Ishida, M. Kudoh, K. Hori, S. Tsuchiya et al. (1994). Selectivity of isoprenoid-containing imidazole antifungal compounds for sterol 14-demethylase P450 (P450(14)DM) and 7-ethoxycoumarin O-deethylase P450 of rat liver microsomes. Biochem. Pharmacol. 48, 1577-1582. 

P-450 or P-450 reductase, induction responses, spectral and binding studies, and microsomal (endoplasmic reticulum) location and requirement for NADPH, O2 etc. (Burke 1981). The induction of a specific isoenzyme of cytochrome P-450 can be detected in crude microsomal preparations by antibodies or MFO reactions specific to that isoenzyme, e.g. the 3-methylcholanthrene (3MC)-inducible type (P4501A subfamily) is detected by the ethoxyresorufin 0-deethylase (EROD) assay (Phillipson et al. 1984,1985 Stegeman et al. 1986). The presence of more than one isoenzyme of cytochrome P-450 in crude microsomes can result in multiphasic kinetics towards a particular substrate, e.g. 7-ethoxycoumarin O-deethylase activity (ECOD) (Lu and West 1980). 

BPH, benzo[a]pyrene hydroxylase (measured fluorometrically except for James and Little (1984) which was radiometric) EROD, 7-ethoxyresorufin O-deethylase ECOD, 7-ethoxycoumarin O-deethylase. 

Large sex differences have been reported in the cytochrome P450 concentration of mouse kidney microsomes and in the hydroxylation of testosterone by kidney microsomes (Hawke etal. 1983, Hawke and Welch 1985). When assayed at 500 j M, male renal 7-ethoxycoumarin-O-deethylase activity was 3-fold greater than female 7-ethoxycoumarin-O-deethylase activity, although this difference was less than that observed in cytochrome P450 concentration as indicated by an approximately 2-fold greater turnover value for female renal microsomes. 

In the human jejunal mucosa semisynthetic (elemental) diets did not change 1-naphthol glucuro-nyltransferase and reductase activities, but significantly depressed 7-ethoxycoumarin 0-deethylase activity (Hoensch etal. 1984). Male subjects had significantly higher ethoxycoumarin 0-deethylase activities than female subjects on semisynthetic... 

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