ArticleDrug metabolism and disposition: the biological fate of chemicals2014
The revised human liver cytochrome P450 "Pie": absolute protein quantification of CYP4F and CYP3A enzymes using targeted quantitative proteomics.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 93 citations in OpenAlex.
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- The curious family of cytochrome P450 4F fatty acid ω-hydroxylases: recent developments in their function and relevance for human health.Open biology · 2025Review
- Age-Dependent Changes in Cytochrome P450 Abundance and Composition in Human Liver.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
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- The desert woodrat (Neotoma lepida) induces a diversity of biotransformation genes in response to creosote bush resin.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2024Article
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- Investigation of doxorubicin combined with ciprofloxacin-induced cardiotoxicity: from molecular mechanism to fundamental heart function.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Using single cell atlas data to reconstruct regulatory networks.Nucleic acids research · 2023Article
- Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.International journal of molecular sciences · 2023Article
- Development of a UPLC-MRM-based targeted proteomic method to profile subcellular organelle marker proteins from human liver tissues.Scientific reports · 2022Article
- The reference liver-CYP450 and UGT enzymes in healthy donor and metastatic livers: the impact of genotype.Pharmacological reports : PR · 2022Article
- Exploring the Interactome of Cytochrome P450 2E1 in Human Liver Microsomes with Chemical Crosslinking Mass Spectrometry.Biomolecules · 2022Article
- Data-independent acquisition (DIA): An emerging proteomics technology for analysis of drug-metabolizing enzymes and transporters.Drug discovery today. Technologies · 2021Review
- Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics.International journal of molecular sciences · 2021Article
- Expression of cytochrome P450 isozyme transcripts and activities in human livers.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- The role of cytochrome P450 (CYP) enzymes in hyperoxic lung injury.Expert opinion on drug metabolism & toxicology · 2021Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
The CYP4F subfamily of enzymes has been identified recently to be involved in the metabolism of endogenous compounds (arachidonic acid and leukotriene B4), nutrients (vitamins K1 and E), and xenobiotics (pafuramidine and fingolimod). CYP4F2 and CYP4F3B are reported to be expressed in the human liver. However, absolute concentrations of these enzymes in human liver microsomes (HLMs) and their interindividual variability have yet to be determined because of the lack of specific antibodies. Here, an liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based targeted quantitative proteomic approach was employed to determine the absolute protein concentrations of CYP4F2 and CYP4F3B compared with CYP3A in two panels of HLMs (n = 31). As a result, the human hepatic cytochrome P450 (P450) "pie" has been revised to include the contribution of CYP4F enzymes, which amounts to 15% of the total hepatic cytochrome P450 enzymes. CYP4F3B displayed low interindividual variability (3.3-fold) in the HLM panels whereas CYP4F2 displayed large variability (21-fold). However, CYP4F2 variability decreased to 3.4-fold if the two donors with the lowest expression were excluded. In contrast, CYP3A exhibited 29-fold interindividual variability in the same HLM panels. The proposed marker reaction for CYP4F enzymes pafuramidine/DB289 M1 formation did not correlate with CYP4F protein content, suggesting alternate metabolic pathways for DB289 M1 formation in HLMs. In conclusion, CYP4F enzymes are highly expressed in the human liver and their physiologic and pharmacologic roles warrant further investigation.
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