Epoxidases metabolism

This epoxidation of AFB has been associated with aldrin epoxidase (AE) activity in trout (30). As with other epoxide carcinogens, OAFB may be a substrate 7or epoxide metabolizing enzyme systems such as epoxide hydrase (EH) (EC4.2.1.63) and glutathione-S-epoxide transferase (GTr) (EC4.4.1.7) found in mammals and fish (31, 32, 33, 34). AFB also undergoes a variety of other reactions, generally to less toxic metabolites depending on the species of animal involved (35, 36). The primary AFB metabolite in rainbow trout has been shown to be a reduced form of AFB, aflatoxicol (AFL) (24). 

Metabolism in Citrus. Recently, Hasegawa et al. (6) have established the presence of a deoxylimonoid pathway in Citrus. Methyl-14c VIII was metabolized in leaves of calamondin to form a deoxy derivative, showing the presence of epoxidase activity which is required for the first step of the deoxylimonoid pathway. Compound XVIII, the product of the second step, was also isolated from grapefruit seeds (6). Furthermore, deoxylimonate A-ring lactone hydrolase, which is involved in the third step of the pathway, was also detected in grapefruit seeds (6). These findings clearly show that limonoids are metabolized in Citrus not only via the 17-dehydrolimonoid pathway as previously established (22), but also via the deoxylimonoid pathway. 

Y Hidaka, H Hotta, Y Nagata, Y Iwasawa, M Horie, T Kamei. Effect of a novel squalene epoxidase inhibitor, NB-598, on the regulation of cholesterol metabolism in Hep G2 cells. J Biol Chem 266 13171-13177, 1991. 

The epoxidase catalyzing the 10,11-epoxidation of methyl farnesoate in homogenates of corpora allata from Locusta miqratoria has been studied in detail and has been shown to be a cytochrome P-450-mediated monooxygenase associated with the microsomal fraction. The enzyme is strictly dependent on NADPH and requires oxygen (36). It is sensitive to inhibition by carbon monoxide (36) and to offier compounds such as methyl enedioxyphenyl compounds and imidazoles that are well established inhibitors of the cytochrome P-450-mediated monooxygenases involved in xenobiotic metabolism (37-39). 

Important for the production of scopolamine, hyoscyamine 6p-hydroxylase was the first enzyme of tropane alkaloid metabolism to be purified and remains the most rigorously studied. It was obtained in pure form from H. niger root cultures and the preparation showed that it is a bifunctional enzyme with activity both as the 7(3-hydroxylase and as the 6,7 3-epoxidase. A clone for H6H was obtained following the purification of enzyme activity. The gene shows some similarity to other hydroxylases, including those involved in oxidative reactions in the formation of ethylene and anthocyanins (Hashimoto and Yamada, 1994). 

A group of fungicides that inhibit squalene epoxidation has been developed primarily for use against pathogenic fungi in medicine. Epoxidation of squalene is catalyzed by squalene epoxidase (a flavoprotein) that starts the complicated cyclization of squalene. The squalene-2,3-epoxide formed by this enzyme is further metabolized to a protosterol cation intermediate, which is transformed to either cycloartenol in plants (cycloartenol synthase) or lanosterol (lanosterol synthase). Cycloartenol is the precursor to plant sterols, whereas lanosterol is the precursor of cholesterol and the other sterols in animals, and to ergosterol in plants. 

Terbinqfine is a synthetic allylamine that is structurally similar to naftifine. It probably acts by inhibiting fungal squalene epoxidase and blocking ergosterol biosynthesis. Terbinafine is well absorbed, but bioavailability is only 40% because of first-pass hepatic metabolism. Proteins bind... 

Terbinafine has a unique action to inhibit squalene epoxidase, causing the intracellular accumulation of squalene to toxic levels. An antidermatophytic agent, terbinafine is used orally and is highly effeetive in onychomyeosis. Its elearance from the body via hepatic metabolism is markedly increased by rifampin. The answer is (D). 

H]IS is metabolized to [ H]24,25-iminolanosterol (IL) which indicates the epoxidase and cyclase are rather non-specific in terms of substrate recognition. (3) 24,25-iminolanosterol (IL) and 25-amino-lanosterol (AL) inhibit C] -transferase activity in g. fu.iikuroi and induce growth inhibition IL is metabolized to AL and an unidentified 4-desmethyl N-containing sterol (m, 397). (4) IS (Fig. 1) but not IL... 

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