1. Flavin monooxygenase (FMO) and cytochrome P450 (CYP450) are both enzymes that are involved in phase I metabolism. They are classified as microsomal enzymes that require oxygen and NADPH. These enzymes are involved in the conversion of lipophilic compounds to more hydrophilic metabolites by adding molecular oxygen, which ensures rapid excretion. There are genetic variants with both classes of enzymes, which may contribute to interindividual variability in drug response.
Some of the differences between properties of these two enzymes include: optimum pH, substrates, heat stability, activating agents, and sensitivity to Mg+2. The optimum pH for FMO is 8.4 and 7.4 to 7.6 for CYP450. Octylamine is the activating agent for FMO and alpha-naphthoflavone for CYP450. FMO is unstable above 40oC, whereas CYP450 is stable up to 60oC. FMO oxygenates soft nucleophiles including: sulfur, nitrogen, or phosphorous heteroatoms, while CYP450 oxidizes these molecules in addition to C-H abstraction. When comparing sensitivity to Mg+2, FMO is inhibited, while CYP450 is stimulated. CYP450 enzyme has a heme iron prosthetic group and FMO enzyme contains flavin adenine dinucleotide (FAD) as a prosthetic group. …show more content…
Flavin-containing monooxygenases (FMOs) enzymes have the ability to metabolize multiple chemicals including: pesticides, drugs, and components of a daily diet. Currently there are five functional FMO isoforms, FMO1-FMO5, that have been identified in humans. In the adult human liver, FMO3 is the most abundantly expressed FMO. Dietary substrates to which FMO3 binds to include tertiary amines: tyramine, trimethylamine, and nicotine. Carbamates and organophosphates found in agrichemicals are also substrates of FMO3. This isoform of FMO can also metabolize a variety of commonly used drugs including amphetamine, cimetidine, clozapine, itopride, ketoconazole, methimazole, sulindac sulfide, and
Some of the differences between properties of these two enzymes include: optimum pH, substrates, heat stability, activating agents, and sensitivity to Mg+2. The optimum pH for FMO is 8.4 and 7.4 to 7.6 for CYP450. Octylamine is the activating agent for FMO and alpha-naphthoflavone for CYP450. FMO is unstable above 40oC, whereas CYP450 is stable up to 60oC. FMO oxygenates soft nucleophiles including: sulfur, nitrogen, or phosphorous heteroatoms, while CYP450 oxidizes these molecules in addition to C-H abstraction. When comparing sensitivity to Mg+2, FMO is inhibited, while CYP450 is stimulated. CYP450 enzyme has a heme iron prosthetic group and FMO enzyme contains flavin adenine dinucleotide (FAD) as a prosthetic group. …show more content…
Flavin-containing monooxygenases (FMOs) enzymes have the ability to metabolize multiple chemicals including: pesticides, drugs, and components of a daily diet. Currently there are five functional FMO isoforms, FMO1-FMO5, that have been identified in humans. In the adult human liver, FMO3 is the most abundantly expressed FMO. Dietary substrates to which FMO3 binds to include tertiary amines: tyramine, trimethylamine, and nicotine. Carbamates and organophosphates found in agrichemicals are also substrates of FMO3. This isoform of FMO can also metabolize a variety of commonly used drugs including amphetamine, cimetidine, clozapine, itopride, ketoconazole, methimazole, sulindac sulfide, and