Nicotinamide N-Oxidation by CYP2E1 in Human Liver Microsomes
Open accessAbstract
Excess nicotinamide, a form of vitamin B(3), is metabolized through two enzymatic systems and eventually excreted from the body. The first system starts with the methylation of nicotinamide by nicotinamide N-methyltransferase, which can subsequently be oxidized by aldehyde oxidase. The second enzymatic system oxidizes nicotinamide to nicotinamide N-oxide. It is located in the endoplasmic reticulum of hepatocytes but the precise enzyme is unknown. We have used human liver microsomes in combination with selective cytochrome P450 inhibitors, specific substrates, and antibodies to identify CYP2E1 as the main activity producing nicotinamide N-oxide. Our results suggest the potential use of nicotinamide N-oxide as a biomarker of CYP2E1 activity from urine or blood samples.
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Excess NAM is oxidized by cytochrome P450 enzyme CYP2E to NAM-N-oxide (oxNAM), which is secreted in urine.
“excess NAM was reported to be oxidized by the cytochrome P450 enzyme CYP2E, converting NAM to NAM-N-oxide (oxNAM), which is also secreted in urine60 (Fig. 7m).”
From Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages (2020) · cites this paper as [60]
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Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages
Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00305-3 · Cited by 420 · see citing works
- Authors
- Real, A. M., Hong, S., & Pissios, P.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Hong, Shangyu
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 41
- Issue
- 3
- Pages
- 550-553
- ISSN
- 0090-9556 (ISSN-L)
- PMC
- PMC3583486
- OpenAlex
- W2160695851
- Cited by
- 44
- References
- 35
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 3 · 2021: 5 · 2020: 2 · 2017: 2 · 2015: 4 · 2014: 1
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK083694)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- nicotinamide N-oxide, CYP2E1, nicotinamide metabolism, human liver microsomes, cytochrome P450, endoplasmic reticulum, nicotinamide N-methyltransferase, aldehyde oxidase, nicotinic acid
- MeSH terms
- Biotransformation, Catalysis, Enzyme Inhibitors, Humans, Kinetics, Liver, Microsomes, Liver, Niacinamide, Oxidation-Reduction, Substrate Specificity, Vitamin B Complex, Cytochrome P-450 CYP2E1, Cytochrome P-450 CYP2E1 Inhibitors
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