Table 1. Key enzymes in Phase 1 and Phase 2 xenobiotic metabolism.

Key enzymes are displayed with corresponding tissue expression information and a selection of known subtypes. General catalytic functions are assigned. The cytochrome P450 Phase 1 enzymes, as well as SULT, UGT, and GST Phase 2 enzymes, play critical roles in the detoxification and metabolism of a wide variety of both endogenous and xenobiotic substances. Bracketed numbers denote references.

Enzyme	Tissue Expression	Subtypes	Function	Ref.
Phase I
Cytochrome P450	Brain Intestine Kydney Liver Lung Skin	1A1, 1A2, 1B1, 2C8, 2C9, 2C18, 2C19, 2D4, 2D6, 2E1, 3A4, 3A5, 3A7, 4A9, 4A11 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, 3A5 1A1, 1A2, 1B1, 2A6, 2B1, 2B2, 2B6, 2C8, 2D6, 2C11, 2E1, 3A1, 3A2, 3A4, 3A5, 4A2, 4A3, 4A11 1A1, 1A2, 2A6, 2B6, 2B7, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 4A9, 4A11 1A1, 1A2, 1B1, 2A6, 2A13, 2B6, 2C9, 2C19, 2D6, 2E1, 2F1, 2S1, 3A4, 3A5, 4B1 1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5	Inducible enzymes that catalyze monooxygenase reactions on many organic endogenous and xenobiotic compounds.	[31, 32, 34–49]
Flavin monooxygenase	Liver, Kidney, Skin	1, 3, 4, 5	Catalyze monooxygenase reactions on nitrogens or amine groups of many xenobiotic substances.
Peroxidases	Liver		Act on organic lipid peroxidases.
Amine Oxidases	Liver		Oxidize primary amines and diamines.
Dehydrogenases	Liver, Skin		Catalyze the oxidation of alcohols, aldehydes, and acetaldehydes for detoxification.
Molybdenum hydroxylase	Liver	Aldehyde oxidases, Xanthine oxidases	Oxidize heterocyclic compounds and aldehydes.	[50]
Esterase/Amidase	Brain, Liver, Skin		Hydrolyze xenobiotic esters and amides.
Epoxide hydrolase	Liver, Lung, Skin		Convert epoxides formed by the metabolism of aromatic compounds into trans-dihydrodiols.
NAD(P)H:quinone reductase	Liver, Skin		Catalyzes oxidoreductive reaction using NADPH for endogenous quinones and some xenobiotics.
Phase 2
Sulfotransferase (SULT)	Brain Intestine kidney Liver Lung Skin	1A1, 1A3, 1E1, 2A1, 4A1 1B1, 1C1, 1C2, 1E1, 2B1 A1, 1A3, 1E 2A1 1A, 1B, 1C, 1E, 2A, 2B 1A1, 1A2 1A1, 1A3	Transfer sulfate groups from 3′-Phosphoadenosine-5′-phosphosulfate to protein or lipids.	[29, 42, 48, 49]
UDP-glucouronosyl transferase (UGT)	Brain Intestine kidney Liver Lung Skin	1A6, 2B7 1A1, 1A3, 1A6, 1A8, 2B7 1A6, 2B7, 2B15, 2B17 1A1, 1A3, 1A4, 1A6, 1A9, 2A1, 2B4, 2B7, 2B15, 2B17 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2A1, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17, 2B28 2B15	Conjugate sugar moieties to many xenobiotics to increase aqueous solubility	[29, 42, 48, 49, 51]
Glutothione-S-Transferase (GST)	Brain Intestine Kidney Liver Lung Skin	pi alpha, pi, mu, theta alpha, pi, theta alpha, pi, mu, theta, omega, zeta, sigma pi pi	Conjugate glutathione to many xenobiotics to increase aqueous solubility	[29, 42, 48, 49, 52–54]
Amino Acid Conjugation	Liver		Conjugation to glycine or other amino acids to exogenous carboxylic acids for excretion.
N-acetyltransferase (NAT)	Liver, Skin	NAT1, NAT2	Transfer acetyl groups from acetyl-co-A to a variety of aromatic compounds.
Methyltransferase	Liver	O-, S-, N-	Transfer methyl group from donor to receptor.
5-nucleotidase	Brain, Liver		Dephosphorylation of deoxy- and ribo- nucleoside monophosphates.
Alkaline phosphatase	Brain, Kidney, Liver		Dephosphorylation of proteins and nucleotides.
γ-Glutamyl Transpeptidase (GGTP)	Brain, Kidney, Liver		Glutathione metabolism and transfer of amino acids across plasma membrane.