Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays

Table 1

Examples of drug metabolizing enzymes (DMEs) [17].

Classification	Enzymes	Overall reactions
Oxidative DMEs (Phase I reactions)	Cytochrome P450 (CYP450)	Carbon oxidation RH + O2 + NADPH + H^+ ROH + H2O + NADP^+
	Flavin-containing monooxygenase (FMO)	N (or S) oxidation R-NH-R′ + O2 + NADPH + H^+ R-NOH-R′ + H2O + NADP^+
	Monoamine oxidase (MAO)	Oxidative deamination R-CH2NH2 + O2 + H2O R-CHO + H2O2 + NH3
	Alcohol dehydrogenase	Alcohol oxidation R-CH2OH + NAD^+ R-CHO + NADH + H^+
	Aldehyde dehydrogenase	Aldehyde oxidation R-CHO + NAD(P)^+ + H2O R-COOH + NAD(P)H + H^+
	Aldehyde oxidase	Aldehyde oxidation R-CHO + O2 + H2O R-COOH + H2O2
Conjugative DMEs (Phase II reactions)	UDP-glycosyltransferase (UGT)	Glucuronidation R + UDP-glucuronic acid R-glucuronide + UDP
	Glutathione S-transferase (GST)	Glutathione conjugation R + GSH GS-RR-X + GSH GS-R + HX
	Sulfotransferase (SULT)	Sulfation R-XH + PAPS R-SO4 + phosphoadenosine + H^+
	N-Acetyltransferase (NAT)	Methylation R-NH2 + CoA-S-COCH3 R-NCOCH3 + CoA-SHR-NHOH + CoA-S-COCH3 R-NHOCOCH3 + CoA-SH

Xenobiotics (R), -nicotinamide adenine dinucleotide phosphate (NADP), -nicotinamide adenine dinucleotide (NAD), uridine 5′-diphosphate (UDP), glutathione (GSH), 3′-phosphoadenosine 5′-phosphosulfate (PAPS), and coenzyme A (CoA).