The involvement of cytochrome P450 (CYP) enzymes in olfaction has been demonstrated in vertebrates over the past decade. In insects, these enzymes are well known for their role in biosynthesis of endogenous compounds as well as xenobiotic metabolism, but the presence of olfactory cytochrome P450s was poorly investigated. Using a PCR-based strategy, we have isolated cDNAs of two new microsomal P450s from the antennae of the cabbage armyworm Mamestra brassicae, CYP9A13 and CYP4G20 of two new microsomal P450s, as well as their red-ox partner, the cytochrome P450 reductase (CPR). Their distribution through the body and their cellular localization within the antennae were studied by RT-PCR and in situ hybridization. The three genes are strongly expressed in some sensory units of the antennae, the sensilla trichodea, which are tuned to odorants detection. The putative functions of the corresponding enzymes are discussed in regard to their respective expression patterns and to our knowledge on olfactory P450 metabolism in mammals.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.gene.2004.11.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lindl. alkaloids improve lipid metabolism by increasing LDL uptake through regulation of the LXRα/IDOL/LDLR pathway and inhibition of PCSK9 expression in HepG2 cells.
Exp Ther Med
March 2025
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China.
Lindl. alkaloids (DNLA) are active ingredients that can be extracted from the traditional Chinese herb Lindl. DNLA exhibits hypoglycemic and antihyperlipidemia effects.
View Article and Find Full Text PDFIsoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples.
Drug Metab Dispos
January 2025
Department of Pharmacotherapy and Translational Research, College of Pharmacy, Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida. Electronic address:
Many factors cause interperson variability in the activity and expression of the cytochrome P450 (CYP) drug-metabolizing enzymes in the liver, leading to variable drug exposure and treatment outcomes. Several liver-enriched transcription factors are associated with CYP expression, with estrogen receptor α (ESR1) and constitutive androstane receptor (CAR or NR1I3) being the 2 top factors. ESR1 and NR1I3 undergo extensive alternative splicing that results in numerous splice isoforms, but how these splice isoforms associate with CYP expression is unknown.
View Article and Find Full Text PDFHeterotropic allosteric modulation of CYP3A4 in vitro by progesterone: Evidence for improvement in prediction of time-dependent inhibition for macrolides.
Drug Metab Dispos
January 2025
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mispredicted (ie, false positives) the interaction that is observed in vivo. Recent findings demonstrated that the presence of the allosteric modulator progesterone (PGS) in the in vitro assay could alter the in vitro kinetics of CYP3A4 TDI with inhibitors that interact with the heme moiety, such as metabolic-intermediate complex forming inhibitors. The impact of the presence of 100 μM PGS on the TDI of molecules in the class of macrolides typically associated with metabolic-intermediate complex formation was investigated.
View Article and Find Full Text PDFEnvironmentally persistent free radicals stimulate CYP2E1-mediated generation of reactive oxygen species at the expense of substrate metabolism.
Drug Metab Dispos
January 2025
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Science Center, New Orleans, Louisiana; The Stanley S. Scott Cancer Center, Louisiana State University Health Science Center, New Orleans, Louisiana. Electronic address:
Environmentally persistent free radicals (EPFRs) are a recently recognized component of particulate matter that cause respiratory and cardiovascular toxicity. The mechanism of EPFR toxicity appears to be related to their ability to generate reactive oxygen species (ROS), causing oxidative damage. EPFRs were shown to affect cytochrome P450 (P450) function, inducing the expression of some forms through the Ah receptor.
View Article and Find Full Text PDFCharacterization of human alcohol dehydrogenase 4 and aldehyde dehydrogenase 2 as enzymes involved in the formation of 5-carboxylpirfenidone, a major metabolite of pirfenidone.
Drug Metab Dispos
January 2025
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan.
Pirfenidone (PIR) is used in the treatment of idiopathic pulmonary fibrosis. After oral administration, it is metabolized by cytochrome P450 1A2 to 5-hydroxylpirfenidone (5-OH PIR) and further oxidized to 5-carboxylpirfenidone (5-COOH PIR), a major metabolite excreted in the urine (90% of the dose). This study aimed to identify enzymes that catalyze the formation of 5-COOH PIR from 5-OH PIR in the human liver.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!