Term
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Definition
Reaction process: hydrolysis of carboxylic acid esters, amides, thioesters
Enzyme: carboxylesterases and acetylcholinesterase (true and psuedo)
Localization of enzyme: serum, erythrocyte membranes
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: hydrolysis of phosphoric acid esters
Enzyme: paraoxonase
Localization of enzyme: serum
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: cleavage of the amide linkage between adjacent amino acids
Enzyme: peptidase
Phase: I
Location of reaction: blood and tissue |
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Term
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Definition
Reaction process: trans-addition of water to alkene epoxides and arene oxides
Enzyme: epoxide hydrolase
Location of enzyme: all tissues
Phase: I
Location of reaction: smooth ER
Notes: 5 forms in mammals |
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Term
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Definition
Reaction process: N=N reduced to 2-NH2 groups (Azo)
Enzyme: CYP450 and NADPH-quinone oxidoreductase
Location of enzyme: all tissues
Phase: I
Location of reaction: GI tract
Notes: catalyzed by intestinal microflora |
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Term
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Definition
Reaction process: N=O reduced to 1-NH2 (Nitro)
Enzyme: CYP450 and NADPH-quinone oxidoreductase
Location of enzyme: all tissues
Phase: I
Location of reaction: GI tract
Notes: catalyzed by intestinal microflora |
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Term
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Definition
Reaction process: aldehydes reduced to primary alcohols/ketones to secondary alcohols (carbonyl)
Enzyme: alcohol dehydrogenase and carbonyl reductase
Location of enzyme: blood and cytosolic fraction of various tissues
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: disulfide reduced by glutathione (GSH)
Enzyme: glutathione S-transferase, glutathione reductase
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: sulfoxide reduction
Enzyme: thioredoxin dependent enzymes
Location of enzyme: liver and kidney cytosol
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: N-Oxide reduction
Enzyme: CYP450 and NADPH-cytochrome P450 reductase
Location of enzyme: liver microsomes
Phase: I
Location of reaction: smooth ER
Notes: NADPH dependent |
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Term
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Definition
Reaction process: quinone reduction to hydroquinone
Enzyme: NADPH-quinone reductase
Location of enzyme: cytosol
Phase: I
Location of reaction: smooth ER
Notes: two electron: catalyzed by carbonyl reductase; one electron catalyzed by NADPH-cytochrome P450 reductase |
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Term
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Definition
Reaction process: Dehalogenation removes halogen (F, Cl, Br, I) from aliphatic xenobiotic
Phase: I
Location of reaction: smooth ER
Notes: three main mechanisms: reductive (H replaces halogen), oxidative (halogen and H on adjacent carbon atom replaced with =O), and double dehalogenation (2 halogens on adjacent carbon atoms form C=C) special form of this is dehydrodechlorination (halogen and hydrogen on adjacent carbon form C=C) |
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Term
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Definition
Reaction process: oxidizes alcohols to aldehydes
Enzyme: alcohol dehydrogenase
Location of enzyme: cytosolic enzyme
Phase: I
Location of reaction: smooth ER
Notes: 4 major classes. Inhibitors are ranitidine, cimetidine, and aspirin |
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Term
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Definition
Reaction process: oxidizes aldehydes to carboxylic acids
Enzyme: aldehyde dehydrogenase
Location of enzyme: cytosolic enzyme
Phase: I
Location of reaction: smooth ER
Cofactor/Cosubstrate: NAD+
Notes: Inhibited by disulfiram; (ALDH 1, 2, and 3) |
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Term
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Definition
Reaction process: oxidize various PAHs
Enzyme: dihydrodiol dehydrogenase
Location of enzyme: cytoplasm, cytosolic enzyme
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: aldehyde oxidase and xanthine oxidase are reduced and then reoxidized by molecular oxygen
Enzyme: molybdenum hydroxylases
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER
Notes: oxygen incorporated into the xenobiotic is derived from water rather than oxygen (oxidases vs. oxygenases); flavoprotein enzymes (XD/XO) |
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Term
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Definition
Reaction process: differ in regard to the electron acceptor used in the final step of catalysis
Enzyme: xanthine dehydrogenase and xanthine oxidase
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER
Notes: flavoprotein enzymes (XD/XO) |
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Term
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Definition
Reaction process: cytosolic aldehyde oxidase transfers electrons to molecular oxygen
Enzyme: aldehyde oxidase
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER
Notes: generates reactive oxygen species and leads to lipid peroxidation; important role in catabolism of biogenic amines and catecholamines |
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Term
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Definition
Reaction process: oxidative deamination of primary, secondary, and tertiary amines
Enzyme: monoamine oxidase (MAOs)
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER |
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Term
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Definition
Reaction process: peroxidases couple oxidation to reduction of H2O2 & lipid hydroperoxidase = cooxidation
Enzyme: peroxidase dependent cooxidation
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER
Notes: prostaglandin H synthetase = cyclooxygenase and peroxidase |
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Term
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Definition
Reaction process: detoxification of xenobiotics, nucleophilic nitrogen, sulfur, and phosphorus heteroatom
Enzyme: flavin monooxygenases (FMO)
Location of enzyme: many tissues; cytosol
Phase: I
Location of reaction: smooth ER
Notes: 5 microsomal enzymes that require NADPH and O2 |
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Term
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Definition
Reaction process: the oxygen atom is reduced to water with the reducing equivalents derived from NADPH
Enzyme: Cytochrome P450
Location of enzyme: many tissues, but highly in liver
Phase: I
Location of reaction: smooth ER
Notes: requires a second enzyme for catalytic activity; P450s catalyze a number of reactions |
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Term
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Definition
Reaction process: UDP-glucuronyltransferase (catalyst) forms O-, N-, S-, C-glucuronides; six forms in human liver
Enzyme: UDP-glucuronyltransferase
Location of enzyme: human liver cytosol
Phase: II
Location of reaction: cytoplasm
Cofactor/Cosubstrate: Cofactor is UDP-glucuronic acid
Notes: inducers: phenobarbital, indoles, 3-methylcholanthrene, cigarette smoking |
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Term
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Definition
Reaction process: produce highly water soluble sulfate esters, eliminated in urine, bile
Enzyme: sulfontranferases
Location of enzyme: human liver cytosol
Phase: II
Location of reaction: cytoplasm
Cofactor/Cosubstrate: cofactor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS)
Notes: xenobiotics and endogenous compounds are sulfated (phenols, catechols, amines, hydroxylamines); Aryl sulfatases in gut microflora remove sulfate groups; enterohepatic recycling delaying elimination; usually decreases pharmacologic, toxic activity |
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Term
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Definition
Reaction process: methyl group (-CH3) bonded to sulfonium ion in SAM is transferred to xenobiotics and endogenous substrates by nuceophilic attack from an electron-rich heteroatom (O, N, S, C)
Enzyme: methyltransferases
Location of enzyme: many tissues; cytosol
Phase: II
Location of reaction: cytoplasm
Cofactor/Cosubstrate: Cofactor: S-adenosylmethionine (SAM); substrates include phenols, catechols, amines, heavy metals (Hg, As, Se)
Notes: decreases water solubility; masks functional groups that might otherwise be conjugated by other Phase II enzymes |
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