A cytochrome P-450 catalysing 25-hydroxylation of vitamin D3 was purified from liver mitochondria of untreated rabbits. The enzyme fraction contained 9 nmol of cytochrome P-450/mg of protein and showed only one protein band with an apparent Mr of 52,000 upon SDS/polyacrylamide-gel electrophoresis. The preparation showed a single protein spot with an apparent isoelectric point of 7.8 and an Mr o...

The metabolism of docetaxel by human liver microsomes was investigated in vitro and compared with that of paclitaxel. A main docetaxel metabolite was generated by human liver microsomes in the presence of NADPH: retention time in high pressure liquid chromatography and its ion fragmentation in mass spectrometry were identical to those of the authentic derivative hydroxylated at the butyl group ...

The oral anticoagulant acenocoumarol is given as a racemic mixture. The (S)-enantiomer is rapidly cleared and is the reason why only (R)-acenocoumarol contributes to the pharmacological effect. The objective of the study was to establish the cytochrome P450 (CYP) enzymes catalyzing the hydroxylations of the acenocoumarol enantiomers. Of various cDNA-expressed human CYPs, only CYP2C9 hydroxylate...

Two hundred thirteen cytochrome P450 (P450) genes were collected from bacteria and expressed based on an Escherichia coli expression system to test their hydroxylation ability to testosterone. Twenty-four P450s stereoselectively monohydroxylated testosterone at the 2alpha-, 2beta-, 6beta-, 7beta-, 11beta-, 12beta-, 15beta-, 16alpha-, and 17-positions (17-hydroxylation yields 17-ketoproduct). Th...

The asparaginyl hydroxylase, factor-inhibiting hypoxia-inducible factor (HIF), is central to the oxygen-sensing pathway that controls the activity of HIF. Factor-inhibiting HIF (FIH) also catalyzes the hydroxylation of a large set of proteins that share a structural motif termed the ankyrin repeat domain (ARD). In vitro studies have defined kinetic properties of FIH with respect to different su...

The cover shows the oxygen diffusion channel in class 7 histone demethylase (PHF8) and ethylene-forming enzyme (EFE). PHF8 catalyzes hydroxylation of its H3 K9me2 substrate, EFE two competing reactions ethylene generation substrate l-Arg hydroxylation. Although both enzymes initially have an off-line 2-oxoglutarate (2OG) conformation, upon binding, forms in-line superoxo complex, whereas uses c...

The cytochrome P-450-dependent drug metabolism system activities of rat colon microsomes are increased by gastroin testinal hormones. Pentagastrin, secretin, and cholecystokinin octapeptide increase the specific content of cytochrome P-450 over control and stimulate /V-demethylation, O-dealkylation, and polycyclic aromatic hydrocarbon hydroxylation to different degrees. Increase in hydroxylatio...

The cytochrome P-450-dependent drug metabolism system activities of rat colon microsomes are increased by gastroin testinal hormones. Pentagastrin, secretin, and cholecystokinin octapeptide increase the specific content of cytochrome P-450 over control and stimulate /V-demethylation, O-dealkylation, and polycyclic aromatic hydrocarbon hydroxylation to different degrees. Increase in hydroxylatio...

It has been known that diclofenac is biotransformed into chemically reactive metabolites, which bind covalently to liver microsomal proteins, including cytochrome P450 enzyme(s). We have investigated the ability and selectivity of diclofenac to inactivate P450 enzymes. Preincubation of microsomes of untreated rats with diclofenac in the presence of NADPH resulted in time-dependent loss of testo...

(+)-S-145 [5-(+)-(Z)-7-[(1R, 2S, 3S, 4S)-3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl]-heptenoic acid] and its beta-oxidized metabolites [two [bisnor or dihydro (DH)-bisnor] or four (tetranor) carbon-shortened products at the carboxyl side chain] are hydroxylated at the C-5 or C-6 position of the bicyclo ring by microsomal monooxygenases. We investigated the oxidative metabolism of (+)-S-145 an...