The major oxidation product of the classic polycyclic hydrocarbon carcinogen benzo(a)pyrene [B(a)P] is 3-hydroxy B(a)P. Numerous studies have been concerned with the measurement of B(a)P 3-hydroxylation activity in experimental animals and human tissues. Although human liver is the main site of this reaction, systematic studies had not been carried out to define the roles of individual cytochro...

Abstract Flavonoids, such as anthocyanins, proanthocyanidins, and flavonols, are widespread plant secondary metabolites important for adaptation to diverse abiotic biotic stresses. Flavonoids can be variously hydroxylated decorated; their biological activity is partly dependent on the degree of hydroxylation B-ring. Flavonoid biosynthesis regulated by MYB transcription factors, which have been ...

The HIF (hypoxia-inducible factor) hydroxylases [PHDs or EGLNs (prolyl hydroxylases), which in humans are PHD isoforms 1-3, and FIH (factor inhibiting HIF)] regulate HIF levels and activity. These enzymes are Fe(II)/2-oxoglutarate-dependent oxygenases, many of which are stimulated by ascorbate. We have investigated the ascorbate dependence of PHD2-catalysed hydroxylation of two prolyl hydroxyla...

The post-translational hydroxylation of prolyl and lysyl residues, as catalyzed by 2-oxoglutarate (2OG)-dependent oxygenases, was first identified in collagen biosynthesis. 2OG oxygenases also catalyze prolyl and asparaginyl hydroxylation of the hypoxia-inducible factors that play important roles in the adaptive response to hypoxia. Subsequently, they have been shown to catalyze N-demethylation...

Enhancement of aniline hydroxylation by Habu snake venom was studied in vitro. The fraction which was isolated from Habu venom through column chromatography caused the enhancement of aniline hydroxylation of hepatic microsomes obtained from untreated rats. This fraction was heat stable and free from phospholipase activity. Enhancement of aniline hydroxylation was not clear in crude Habu venom o...

The metabolism of some steroids has been investigated in liver microsomal preparations from male germ-free and conventional rats. Hydroxylation of 4-[4-14C]androstene3,17-dione in positions 60 and 16~~ is about 2 and 1.5 times more efficient in germ-free than in conventional rats. The same is true for 6/3and Zol-hydroxylation of 4-[4J4C]pregnene-3,20-dione (about 1.6 and 1.2 times larger, respe...

(-)-Verbenone, a monoterpene bicyclic ketone, is a component of the essential oil from rosemary species such as Rosmarinus officinalis L., Verbena triphylla, and Eucalyptus globulus and is used for an herb tea, a spice, and a perfume. In this study, (-)-verbenone was found to be converted to 10-hydroxyverbenone by rat and human liver microsomal cytochrome p450 (p450) enzymes. The product format...

In rats, six cytochrome P450 (P450) 2D isoforms have been genetically identified. Nonetheless, there is little evidence of catalytic properties of each CYP2D isoform. In this study, using recombinant CYP2D isoforms (rat CYP2D1, CYP2D2, CYP2D3, and CYP2D4 and human CYP2D6) or hepatic microsomes, we investigated the catalytic specificity toward bufuralol, debrisoquine, and propranolol, which are ...

A novel method for α-hydroxylation of ketones using substoichiometric amount of iodine under metal-free conditions is described. This method has been successfully employed in synthesizing a variety of heterocyclic compounds, which are useful precursors. α-Hydroxylation of diketones and triketones are illustrated. This strategy provides a novel, efficient, mild and inexpensive method for α-hydro...

Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. ...