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Drug Metabolizing Enzymes

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Abstract

Metabolism is the major elimination pathway of a drug from the body. Drug metabolizing enzymes (DMEs) are mainly present in the liver, intestine, and blood and are responsible for converting lipophilic drugs to more hydrophilic compounds to facilitate their excretion from the body. DMEs are classified as either Phase I or Phase II enzymes. Phase I DMEs are responsible for oxidation, reduction, and hydrolysis, and Phase II DME are responsible for conjugation (not necessarily sequential). Here we discuss the DMEs involved in Phase I and Phase II reactions, their subcellular locations, cofactors, organ distributions, mechanisms of reactions, and typical substrates and inhibitors.

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Abbreviations

ABT:

Aminobenzotriazole

ADH:

Alcohol dehydrogenase

AKR:

Aldo-keto reductase

ALDH:

Aldehyde dehydrogenase

AO:

Aldehyde oxidase

AZT:

3′-Azido-3′-deoxythimidine

BSO:

l-Buthionine-sulfoximine

CDNB:

1-Chloro-2,4-dinitrobenzene

CL:

Clearance

DCNP:

2,6-Dichloro-4-nitrophenol

DME:

Drug metabolizing enzyme

EC:

Enzyme classification number based on enzyme function

EH:

Epoxide hydrolase

ER:

Endoplasmic reticulum (i.e., microsomes)

FAD:

Flavin adenine dinucleotide

FMO:

Flavin-containing monooxygenase

GI:

Gastrointestinal

GST:

Glutathione S-transferase

LM:

Liver microsomes

MAO:

Monoamine oxidase

mCPBA:

m-Chloroperoxybenzoic acid

NAC:

N-Acetylcysteine

NAD:

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NAT:

N-Acetyltransferase

P450:

Cytochrome P450

PAPS:

3′-Phosphoadenosine-5′-phosphosulfate

PM:

Poor metabolizer

NQO:

NADPH:quinone reductase

SAM:

S-Adenosyl methionine

SULT:

Sulfotransferase

UDPGA:

Uridine diphosphoglucuronic acid

UGT:

Uridine diphosphate glucuronosyltransferase

XDH:

Xanthine dehydrogenase

XO:

Xanthine oxidase

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Authors and Affiliations

  1. Genentech, Inc., 1 DNA Way, San Francisco, California, USA

    Siamak Cyrus Khojasteh, Harvey Wong & Cornelis E. C. A. Hop

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  1. Siamak Cyrus Khojasteh
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  2. Harvey Wong
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  3. Cornelis E. C. A. Hop
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Correspondence to Siamak Cyrus Khojasteh .

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Khojasteh, S.C., Wong, H., Hop, C.E.C.A. (2011). Drug Metabolizing Enzymes. In: Drug Metabolism and Pharmacokinetics Quick Guide. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5629-3_2

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