The hydroxylation and N-dechloroethylation of deuterated ifosfamide (d4IFO) and ifosfamide (IFO) by several human P450s have been determined and compared. d4IFO was synthesized with deuterium at the alpha and alpha9 carbons to decrease the rate of N-dechloroethylation and thereby enhance hydroxylation of the drug at the 49 position. The purpose was to decrease the toxic and increase the efficac...

Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to le...

Western blot analyses of liver microsomes from 13 male and 12 female monkeys demonstrated that in each sample a variable amount of a cytochrome P450 (P450) protein, likely monkey P450 2E1, cross-reacted with anti-rat P450 2E1 antibodies. Therefore, the involvement of monkey 2E1 in the oxidation of typical substrates for 2E1 from other species, such as dimethylnitrosamine (DMN), p-nitrophenol (p...

Roxithromycin has been shown to be a relatively weak inhibitor of cytochrome P450 (P450 or CYP)-dependent drug oxidations, compared with troleandomycin. The potential for roxithromycin and its major metabolites found in human urine [namely the decladinosyl derivative (M1), O-dealkyl derivative (M2), and N-demethyl derivative (M3)] to inhibit testosterone 6beta-hydroxylation after metabolic acti...

We have previously shown racial differences in propranolol kinetics, with the largest differences appearing to be in its 4-hydroxylation. The purpose of this study was to identify and confirm the cytochrome P450 enzymes (CYP) with propranolol 4-hydroxylase activity, describe their enzyme kinetics, and determine whether there were racial differences in their catalytic activity. Eleven human reco...

Our previous studies, carried out using rat cDNA-expressed cytochrome P450 (CYP) isoforms, liver microsomes and specific CYP inhibitors, showed that the 1-N- and 3-N-demethylation of caffeine at a therapeutic concentration was predominantly catalyzed by CYP1A2 and CYP2C, its 7-N-demethylation was governed by P450s of the CYP2C subfamily, while its 8-hydroxylation was specifically mediated by CY...

Cytosine-5-methylation stabilises DNA duplexes and is associated with transcriptional repression; 5-methylcytosine undergoes hydroxylation to 5-hydroxymethylcytosine, a modification of unknown biological function. Spectroscopic and calorimetric analyses show that 5-hydroxymethylcytosine introduction reverses the stabilising effect of 5-methylcytosine, suggesting that in some contexts, 5-methylc...

Polyolefins account for 60% of global plastic consumption, but many potential applications of polyolefins require that their properties, such as compatibility with polar polymers, adhesion, gas permeability, and surface wetting, be improved. A strategy to overcome these deficiencies would involve the introduction of polar functionalities onto the polymer chain. Here, we describe the Ni-catalyze...

Cell-free particulate fractions derived from methylotrophic bacteria catalyze the oxygen- and reduced nicotinamide adenine dinucleotide-dependent epoxidation of alkenes and hydroxylation of alkanes. Evidence presented indicates that the hydroxylation and epoxidation reactions are catalyzed by the same or a similar metal-containing monooxygenase.

Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite formation have not been identified. In this study, we used human liver microsomes and recombinant cyto...