title: Nicotinamide N-oxidation by CYP2E1 in human liver microsomes.
abstract: 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.
authors: Endocrinology, Diabetes, and Metabolism, E/CLS-735, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors: Alexander Michael
authors: AM
authors: Real
authors: Shangyu
authors: S
authors: Hong
authors: Pavlos
authors: P
authors: Pissios
mesh_terms: D001711:Biotransformation; D002384:Catalysis; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism*; D010084:Oxidation-Reduction; D013379:Substrate Specificity; D014803:Vitamin B Complex / Q000378:metabolism*
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D014803:Vitamin B Complex; D009536:Niacinamide; C037645:nicotinamide N-oxide; D019392:Cytochrome P-450 CYP2E1