Phase I NON-P450 Reactions Flashcards
What are non-P450-mediated Phase I reactions?
These are metabolic reactions that do not involve cytochrome P450 enzymes and include oxidation, reduction, and hydrolysis reactions.
What enzymes are involved in non-P450-mediated oxidation?
Enzymes include alcohol dehydrogenase, flavin monooxygenase (FMO), monoamine oxidase (MAO), aldehyde oxidase (AO), and xanthine oxidase (XO).
What is alcohol oxidation and its example?
Alcohol oxidation involves converting primary or secondary alcohols to aldehydes or ketones. For example, ethanol is oxidized to acetaldehyde by alcohol dehydrogenase using NAD⁺.
What is N-oxidation and its example?
N-oxidation involves oxidizing secondary or tertiary amines to produce N-oxides. For example, nicotine is oxidized to nicotine-1-oxide by flavin monooxygenase (FMO).
What is S-oxidation and its example?
S-oxidation involves oxidizing thiols to sulfoxides or sulfones. An example is the oxidation of sulindac to sulindac sulfoxide by methionine sulfoxide reductase.
What is the role of monoamine oxidase (MAO) in drug metabolism?
MAO catalyzes the oxidative deamination of neurotransmitters and certain drugs. For example, sumatriptan is metabolized by MAO-A to an indole-acetic acid derivative.
What is aldehyde oxidation and its example?
Aldehyde oxidation involves converting aromatic aldehydes to carboxylic acids. For example, benzaldehyde is oxidized to benzoic acid by aldehyde oxidase (AO), producing hydrogen peroxide (H₂O₂) as a by-product.
What is xanthine oxidation and its example?
Xanthine oxidation involves oxidizing purines. For example, 6-mercaptopurine is metabolized to 6-thiouric acid (inactive) by xanthine oxidase (XO).
What are reductive reactions and their importance?
Reduction reactions add hydrogen or remove oxygen, creating polar functional groups for excretion. These reactions include nitro reduction, sulfoxide reduction, and epoxide reduction.
What is nitro reduction and its example?
Nitro reduction involves converting nitro groups (-NO₂) to amines. For example, clonazepam is reduced to 7-amino clonazepam by nitroreductases in gut microflora.
What is sulfoxide reduction and its example?
Sulfoxide reduction involves converting sulfoxides (S=O) to sulfides. For example, sulindac is reduced to its active form, sulindac sulfide, by methionine sulfoxide reductase.
What is epoxide reduction and its example?
Epoxide reduction involves converting epoxides to diols. For example, vitamin K epoxide is reduced to vitamin K hydroquinone by epoxide reductase.
What are hydrolytic reactions in Phase I metabolism?
Hydrolysis involves cleaving chemical bonds using water. Key enzymes include carboxylesterase, paraoxonase, and alkaline phosphatase.
What is ester hydrolysis and its example?
Ester hydrolysis converts esters to alcohols and carboxylic acids. For example, heroin is hydrolyzed to morphine by carboxylesterase.
What is amide hydrolysis and its example?
Amide hydrolysis converts amides to carboxylic acids and amines. For example, procainamide is hydrolyzed to p-aminobenzoic acid by carboxylesterase.
