Functionalization: Phase I Oxidation and Reduction Quiz

Phase I reactions like oxidation and reduction prepare a lipophilic drug for Phase II conjugation by adding or exposing groups like hydroxyl or carboxyl. This increases the overall polarity and reactivity of the molecule.

The unique absorption at 450 nm in the reduced carbon monoxide bound state is characteristic of these heme containing enzymes and is used to quantify enzyme concentration in microsomes.

The iron atom cycles between the ferric Fe3 and ferrous Fe2 states during the catalytic cycle facilitating the activation of molecular oxygen for insertion into the drug substrate.

The P450 system is a multicomponent electron transport chain. It requires NADPH as an electron donor a reductase enzyme to transfer those electrons and atmospheric oxygen to provide the oxygen atom.

Cytochrome P450s are monooxygenases. They split O2 incorporating one oxygen atom into the drug and reducing the other atom with electrons and protons to form a molecule of H2O.

The P450 enzyme inserts oxygen into the aromatic ring to form an epoxide. This intermediate can then rearrange into a phenol or be targeted by epoxide hydrolase enzymes.

FMOs use FAD as a cofactor rather than heme iron. They are particularly important for the N oxidation of tertiary amines and the S oxidation of thioethers.

Dealkylation involves the removal of alkyl groups from nitrogen or oxygen atoms often revealing a more polar group. Glucuronidation is a Phase II conjugation reaction.

During oxidative deamination the C N bond is cleaved. The carbon atom is oxidized to a carbonyl group and the nitrogen is released as ammonia or a primary amine.

Reductive reactions are most common in low oxygen environments such as the lower gastrointestinal tract by gut microflora or in the liver when oxygen tension is very low.

Azo reductase enzymes split the nitrogen nitrogen double bond by adding electrons and protons eventually breaking the molecule into two separate aromatic amines.

Metronidazole and chloramphenicol contain nitro groups that are reduced to hydroxylamines or amines which is often essential for their therapeutic or toxic effects.

ADH is a cytosolic enzyme that uses NAD as a cofactor to oxidize alcohols. This is the primary pathway for the metabolism of ethanol in the human body.

Induction increases the synthesis of P450 enzymes. This speeds up the metabolism of any drug that is a substrate for those enzymes leading to lower therapeutic levels.

Poor metabolizers lack functional copies of the enzyme. If a drug is cleared by that specific enzyme it will accumulate in the body significantly increasing the risk of toxicity.