ArticleChemical research in toxicology2011
Cytochromes P450 catalyze the reduction of α,β-unsaturated aldehydes.
Article in Chemical research in toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Cytochrome P450The Journal of biological chemistry · 2025Article
- Exploring Secondary Amine Carnosine Derivatives: Design, Synthesis, and Properties.Molecules (Basel, Switzerland) · 2024Article
- Reactive Carbonyl Species Scavenger: Epigallocatechin-3-Gallate.Foods (Basel, Switzerland) · 2024Review
- Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.Chemical reviews · 2018Review
- High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities.Chemical research in toxicology · 2018Article
- CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.Environment international · 2017Observational
- Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Article
- 4-Hydroxy-nonenal-A Bioactive Lipid Peroxidation Product.Biomolecules · 2015Review
- S-adenosyl-l-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry.Toxicology and applied pharmacology · 2014Article
- Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats.Toxicology and applied pharmacology · 2014Article
- Comparative metabolism of furan in rodent and human cryopreserved hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- A targeted proteomics approach for profiling murine cytochrome P450 expression.The Journal of pharmacology and experimental therapeutics · 2014Article
- Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.Toxicology and applied pharmacology · 2014Article
- Reactive metabolites in the biotransformation of molecules containing a furan ring.Chemical research in toxicology · 2013Review
- Article
- Protein modification by oxidized phospholipids and hydrolytically released lipid electrophiles: Investigating cellular responses.Biochimica et biophysica acta · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The metabolism of α,β-unsaturated aldehydes, e.g., 4-hydroxynonenal, involves oxidation to carboxylic acids, reduction to alcohols, and glutathionylation to eventually form mercapturide conjugates. Recently, we demonstrated that P450s can oxidize aldehydes to carboxylic acids, a reaction previously thought to involve aldehyde dehydrogenase. When recombinant cytochrome P450 3A4 was incubated with 4-hydroxynonenal, O(2), and NADPH, several products were produced, including 1,4-dihydroxynonene (DHN), 4-hydroxy-2-nonenoic acid (HNA), and an unknown metabolite. Several P450s catalyzed the reduction reaction in the order (human) P450 2B6 ≅ P450 3A4 > P450 1A2 > P450 2J2 > (mouse) P450 2c29. Other P450s did not catalyze the reduction reaction (human P450 2E1 and rabbit P450 2B4). Metabolism by isolated rat hepatocytes showed that HNA formation was inhibited by cyanamide, while DHN formation was not affected. Troleandomycin increased HNA production 1.6-fold while inhibiting DHN formation, suggesting that P450 3A11 is a major enzyme involved in rat hepatic clearance of 4-HNE. A fluorescent assay was developed using 9-anthracenealdehyde to measure both reactions. Feeding mice a diet containing t-butylated hydroxyanisole increased the level of both activities with hepatic microsomal fractions but not proportionally. Miconazole (0.5 mM) was a potent inhibitor of these microsomal reduction reactions, while phenytoin and α-naphthoflavone (both at 0.5 mM) were partial inhibitors, suggesting the role of multiple P450 enzymes. The oxidative metabolism of these aldehydes was inhibited >90% in an Ar or CO atmosphere, while the reductive reactions were not greatly affected. These results suggest that P450s are significant catalysts of the reduction of α,β-unsaturated aldehydes in the liver.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.