Six of the cytochrome P450 enzymes metabolize 90% of all drugs and require as a cofactor
The correct answer and explanation is:
The correct answer is NADPH.
Cytochrome P450 enzymes are a large family of enzymes involved in the metabolism of a wide range of substances, including drugs, toxins, and endogenous compounds. These enzymes are primarily located in the liver and play a critical role in the phase I metabolism of drugs, often by oxidizing or reducing the compounds.
There are six major cytochrome P450 enzymes, known as CYP3A4, CYP2C9, CYP2C19, CYP1A2, CYP2D6, and CYP2E1, which together are responsible for the metabolism of approximately 90% of all pharmaceutical drugs. These enzymes function through the process of hydroxylation, which involves the addition of an oxygen atom to a substrate, often converting lipophilic compounds into more hydrophilic forms, making them easier to excrete from the body.
Cytochrome P450 enzymes require NADPH (nicotinamide adenine dinucleotide phosphate) as a cofactor in their catalytic cycle. NADPH provides the necessary reducing equivalents (electrons) for the cytochrome P450 enzymes to carry out oxidation reactions. Specifically, NADPH is used by a reductase enzyme, which transfers electrons to the cytochrome P450 enzyme, enabling it to perform the oxidative metabolism of drugs and other substrates.
These enzymes also require molecular oxygen (O₂) for their reactions, but NADPH is essential for the reduction process within the enzyme’s active site, ensuring the successful metabolism of the drug or other compound. In addition to NADPH, cytochrome P450 enzymes work in conjunction with other cofactors such as heme, which binds to the oxygen and facilitates the electron transfer necessary for the enzyme to function.
In summary, NADPH is crucial in the metabolism of drugs by cytochrome P450 enzymes as it provides the reducing power required for their enzymatic activities.