Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver microsomes from control and treated rats (P4501A, 2B, 2E1-induced) metabolize at variable metabolic rates eight N-nitroso-di-n-alkylamines, including five symmetrical (N-nitroso-dimethyl, -diethyl, -dipropyl, -dibutyl and -diamyl-amines) and four asymmetrical (N-nitrosomethylethyl, methylpropyl, methylbutyl, and methylamyl-amines), into aldehydes. Thus, the longer the alkyl chain of symmetrical N-nitrosamines, the smaller was the metabolic rate of the corresponding aldehyde formation. The chain length of the alkyl group of N-nitroso-methylalkylamines modified the oxidation of the alkyl moiety: the oxidation by CYP2E1 decreased as the n-alkyl chain length increased and conversely for the oxidation by CYP1A and CYP2B. Finally, the longer the n-alkyl chain length of asymmetrical N-nitrosamines, the greater was the oxidation of methyl groups.
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PMID:Effect of the length of alkyl chain on the cytochrome P450 dependent metabolism of N-diakylnitrosamines. 862 Apr 30

Accumulated evidence suggests that cross-talk between the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) results in shared transcriptional activation of CYP2B and CYP3A genes. Although most data imply symmetrical cross-regulation of these genes by rodent PXR and CAR, the actual selectivities of the corresponding human receptors are unknown. The objective of this study was to evaluate the symmetry of human (h) PXR and hCAR cross-talk by comparing the selectivities of these receptors for CYP2B6 and CYP3A4. Human hepatocyte studies revealed nonselective induction of both CYP2B6 and CYP3A4 by hPXR activation but marked preferential induction of CYP2B6 by selective hCAR activation. Gel shift assays demonstrated that hPXR exhibited strong and relatively equal binding to all functional response elements in both CYP2B6 and CYP3A4 genes, whereas hCAR displayed significantly weak binding to the CYP3A4 proximal ER6 motif. In cell-based transfection assays, hCAR displayed greater activation of CYP2B6 reporter gene expression compared with CYP3A4 with constructs containing both proximal and distal regulatory elements. Furthermore, in agreement with binding observations, transfection assays using promoter constructs containing repeats of CYP2B6 DR4 and CYP3A4 ER6 motifs revealed an even greater difference in reporter activation by hCAR. In contrast, hPXR activation resulted in less discernible differences between CYP2B6 and CYP3A4 reporter gene expression. These results suggest asymmetrical cross-regulation of CYP2B6 and CYP3A4 by hCAR but not hPXR in that hCAR exhibits preferential induction of CYP2B6 relative to CYP3A4 because of its weak binding and functional activation of the CYP3A4 ER6.
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PMID:Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor. 1651 49