Cytochrome P450 CYP isoforms

Metabolism - In vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism mediated by any of the following cytochrome P450 (CYP) isoforms 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. 

Shin, J.G., Soukhova, N., and Flockhart, D.A. (1999) Effect of antipsychotic drugs on human liver cytochrome P450 (CYP) isoforms in vitro preferential inhibition of CYP2D6. Drug Metab Dfspos 27 1078-1084. 

Methods for estimating these corrections for cytochrome P450 (CYP) isoforms have been patented by the Camitro Corporation. The use of quantum mechanical (QM) methods in metabolism prediction thus varies in complexity. The simplest use is from the examination of empirical correlations of enzymic specific activity (pmol/min mg enzyme) with a single parameter such as the energy of the lowest unoccupied molecular orbital (ELUM0). 

Kobayashi, K., K. Urashima, N. Shimada, and K. Chiba (2002). Substrate specificity for rat cytochrome P450 (CYP) isoforms Screening with cDNA-expressed systems of the rat. Biochem. Pharmacol. 63, 889-896. 

Redlich G, Zanger UM, Riedmaier S, Bache N, Giessing AB, Eisenacher M, Stephan C, Meyer HE, Jensen ON, Marcus K (2008) Distinction between human cytochrome P450 (CYP) isoforms and identification of new phosphorylation sites by mass spectrometry. J Proteome Res 7 4678-4688... 

Table 13.1 Cytochrome P450 (CYP) isoforms and metabolites. The CYPs that catalyze the co-hydroxylation of ara-chidonie aeidto 16-, 17-, 18-, 19-, and 20-HETE are displayed ...

Omeprazole is mainly metabolized by cytochrome P450 (CYP 2C19). This enzyme is expressed polymorphically, which means that some individuals do not express a functioning CYP 2C19 enzyme. In these individuals, another CYP isoform (CYP 3A4), which normally plays a less dominant role in the metabolism of... 

Phase I oxidation generally is described as the addition of an oxygen atom (e.g., as an hydroxyl moiety) to the parent molecule. Phase I oxidation is carried out by multiple enzyme pathways, including the various isoforms of the cytochrome P450 (CYP) family and the non-P450 biotransformation enzymes such as flavin-containing monooxygenase (FMO) and monamine oxidase (MAO). 

Allelic variants for other CYP isoforms involved in the metabolism of drugs have been documented and in some cases effects of allelic variants have been examined. A compendium of allelic variants for human CYP isoforms in families 1, 2, 3, and 4 is available on the Web at the home page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (http //www.cypaheles.ki.se/cypalleles.html). 

CYP. .. Cytochrome P450 enzyme isoforms NK2 Neurokinin receptor, type 2 (receptor for neurokinin A)... 

As reported by Russel et al., carried out metabolic smdies showed that pyrethroids are mainly metabolized by oxidation and ester cleavage, which are mediated by cytochrome isoforms and carboxylesterases, respectively (Russel et al. 2011). The biodegradation of synthetic pyrethroids is involved in the resistance of insects, in addition carboxylesterases, cytochromes P450 (CYPs) and GSTs (glutathione-5 -transferases) have all been implicated in this resistance. Intense bands of carboxy-lesterase activity in nondenaturing polyacrylamide gel had been associated with resistance to synthetic pyrethroids in various species, however, resistance... 

Cytochrome P450 (EC 1.14.14.1) enzymes are well known for their ability to metabolize the majority of drugs, to detoxify environmental pollutants, and to activate some classes of carcinogens [93]. The most highly expressed subfamily is CYP 3A, which includes the isoforms CYP 3A4, CYP 3A5, CYP 3A7, and CYP 3A43 [93, 94]. The most abundant isoform is CYP 3A4, which corresponds to 30% of the total P450 content in the liver and about 70% of the total P450 content in the... 

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