Updated models of the Rat Cytochrome P450 2D enzymes are produced based on the recent x-ray structures of the Human P450 2D6 enzyme both with and without a ligand bound. The differences in species selectivity between the epimers quinine and quinidine are rationalised using these models and the results are discussed with regard to previous studies. A close approach to the heme is not observed in...

UNLABELLED Ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome P450 enzymes (Erg proteins) that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. However, the opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome P450 enzyme Cy...

Cytochrome P450 (P450) protein-protein interactions have been observed with various in vitro systems. It is interesting to note that these interactions seem to be isoform-dependent, with some combinations producing no effect and others producing increased or decreased catalytic activity. With some exceptions, most of the work to date has involved P450s from rabbit, rat, and other animal species...

Xanthates (alkyl or aryl derivatives of dithiocarbonic acid) have been shown to be selective mechanism-based inactivators of cytochromes P450 2B1/2B6 and 2E1 due to covalent binding of a reactive intermediate to apoprotein after double hydrogen abstraction at α-carbon atom, suggesting interaction of the xanthate dithiocarbonic head with the enzyme heme. The structures of xanthates with a long a...

CYP83B1 from Arabidopsis thaliana has been identified as the oxime-metabolizing enzyme in the biosynthetic pathway of glucosinolates. Biosynthetically active microsomes isolated from Sinapis alba converted p-hydroxyphenylacetaldoxime and cysteine into S-alkylated p-hydroxyphenylacetothiohydroximate, S-(p-hydroxyphenylacetohydroximoyl)-l-cysteine, the next proposed intermediate in the glucosinol...

The selectivity of inhibition for four dopamine receptor agonists (pramipexole, ropinirole, pergolide, and bromocriptine) on six human cytochrome P450 enzyme activities were evaluated using a simple in vitro inhibition screen. Drug-P450 interactions characterized as potent (i.e. greater than 50% inhibition of control enzyme activity) were then further examined to determine an IC50 for the inter...

To the Editors: McFadyen et al. (1) have contributed a review on the aspects of cytochrome P450–related tumor therapy that is worth reading. It clearly shows the potential of such an approach for cancer therapy. Based on my own experience, I would kindly like to point out a few additional issues that may add to the excellent review. Ifosfamide and cyclophosphamide both use some more cytochrome ...

Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activi...

Cytochrome P450 (CYP) monooxygenases catalyze the oxidation of a large number of endogenous compounds and the majority of ingested environmental chemicals, leading to their elimination and often to their metabolic activation to toxic products. This enzyme system therefore provides our primary defense against xenobiotics and is a major determinant in the therapeutic efficacy of pharmacological a...

Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse. These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4).. .. Covera HS, Isoptin SR, Verelan); Warfarin (coumadin); Zolpidem (Ambien): Little or no interaction with grapefruit juice. The aim of this study was to identify the form(s) of cytochrome P450 (CYP) responsibl...