We have studied the effect of propofol on the cytochrome P450-dependent mono-oxygenase system in human liver microsomes by assaying mono-oxygenase activities toward specific cytochrome P450 isoform test substrates, aniline, 7-ethoxycoumarin, benzphetamine and benzo(a) pyrene. Propofol inhibited benzo(a)pyrene hydroxylation to a greater extent than the oxidative metabolism of the other test subs...

NADPH-cytochrome c reductase was solubilized from the microsomal fraction of Petunia hybrida flowers by 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate detergent and purified by adenosine 2',5'-bisphosphate-Sepharose chromatography, followed by high-performance anion-exchange chromatography. Two proteins with molecular sizes of 75 and 81 kD were detected in the purified preparation b...

Squalene monooxygenase is a microsomal enzyme that catalyzes the conversion of squalene to 2,3(s)-oxidosqualene, the immediate precursor to lanosterol in the cholesterol biosynthesis pathway. Unlike other flavoprotein monooxygenases that obtain electrons directly from NAD(P)H, squalene monooxygenase requires a redox partner, and for many years it has been assumed that NADPH-cytochrome P450 redu...

dacarbazine (dtic) is a synthetic chemical antitumor agent which is used to treat malignant melanoma and hodgkin’s disease. dtic is a prodrug which is converted to an active form undergoing demethylation by liver enzymes. the active form prevents the progress of disease via alkylation of dna strand. in the structure of this drug, the imidazole ring, a triazen chain and carboxamide group exist. ...

Mammalian cytochrome 1'-450 exists as a multigene family expressing a spectrum of structurally and functionally distinct isoenzymes involved in the biotransformation of both exogenous and endogenous substrates [ l , 21. Although a generally accepted isoenzyme nomenclature based on divergent evolution and nucleotide/amino acid homologies is now widely used [I], i t is still useful, under certain...

The role of cytochrome b(5) (b(5)) in the alpha-naphthoflavone (alpha-NF)-mediated inhibition of H(2)O(2)-supported 7-benzyloxyquinoline (7-BQ) debenzylation by heterologously expressed and purified cytochrome P450 3A4 (CYP3A4) was studied. Although alpha-NF showed negligible effect in an NADPH-dependent reconstituted system, inhibition of 7-BQ oxidation was observed in the H(2)O(2) system. Ana...

In this study, we investigated the enzymes catalyzing the phase I metabolism of thiacalixarene (TCAS) based on in vitro system including cDNA-expressed P450 enzymes, human liver microsomes plus inhibitors and monoclonal antibodies. In addition, the inhibitory potential of TCAS on major CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2B6, CYP2D6 and CYP3A4) was assessed. The results showed ...

Using human liver microsomes (HLMs) and recombinant human cytochrome P450 (CYP450) isoforms, we identified the major route of pimozide metabolism, the CYP450 isoforms involved, and documented the inhibitory effect of pimozide on CYP450 isoforms. Pimozide was predominantly N-dealkylated to 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one (DHPBI). The formation rate of DHPBI showed biphasic ki...

OBJECTIVES Cytochrome P450 (CYP) 1A1 located in the membrane of endoplasmic reticulum is the most important enzyme in both activation and detoxification of carcinogenic benzo[a]pyrene (BaP), in combination with microsomal epoxide hydrolase (mEH). However, it is still not clearly explained how the electron transfer is mediated by NADPH:CYP oxidoreductase (POR), another component of the microsoma...

We investigated the effect of an albumin infusion on enzyme activity, expression level cytochrome P450 2E1 (CYP2E1), and oxidative stress in serum liver streptozotocin (STZ)-induced diabetic rats. The STZ treatment enhanced alanine aminotransferase aspartate activities rat compared with those untreated Treatment elevated catalytic activity CYP2E1, stress, decreased reducing potentials liver, su...