Abstract
Excess nicotinamide, a form of vitamin B3, 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.
Footnotes
This research was supported by the National Institutes of Health [Grant 5R01DK083694].
- Received October 18, 2012.
- Accepted December 20, 2012.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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