Cytochrome P450 enzymes
Cytochrome P450 enzymes
Most of the Phase I reactions are caused by the cytochrome P450 microsomal oxidase system. There are 18 families of cytochrome P450 genes with 43 subfamilies (more genes have been identified but their function is unknown). Each enzyme is identifiable by the abbreviation CYP followed by the class (number) and then subfamily (letter) and gene (number).
CYP 1, 2, 3 families are known to metabolize lipophilic drugs and the most important 8 are shown in the figure. The remaining enzymes synthesize or degrade other lipophilic compounds such as cholesterol, bile acids, hormones, etc.
It is often important to know if a drug is a “substrate”, “inhibitor” or “inducer” of a particular enzyme system.
Cytochrome P450 enzymes
Most of the Phase I reactions are caused by the cytochrome P450 microsomal oxidase system. There are 18 families of cytochrome P450 genes with 43 subfamilies (more genes have been identified but their function is unknown). Each enzyme is identifiable by the abbreviation CYP followed by the class (number) and then subfamily (letter) and gene (number).
CYP 1, 2, 3 families are known to metabolize lipophilic drugs and the most important 8 are shown in the figure. The remaining enzymes synthesize or degrade other lipophilic compounds such as cholesterol, bile acids, hormones, etc.
It is often important to know if a drug is a “substrate”, “inhibitor” or “inducer” of a particular enzyme system.
Cytochrome P450 enzymes
Most of the Phase I reactions are caused by the cytochrome P450 microsomal oxidase system. There are 18 families of cytochrome P450 genes with 43 subfamilies (more genes have been identified but their function is unknown). Each enzyme is identifiable by the abbreviation CYP followed by the class (number) and then subfamily (letter) and gene (number).
CYP 1, 2, 3 families are known to metabolize lipophilic drugs and the most important 8 are shown in the figure. The remaining enzymes synthesize or degrade other lipophilic compounds such as cholesterol, bile acids, hormones, etc.
It is often important to know if a drug is a “substrate”, “inhibitor” or “inducer” of a particular enzyme system.
A patient (54-year-old) is treated with metoprolol (beta-blocker). Metoprolol is metabolized in the liver by CYP2D6 into inactive metabolites. After a genetic test, the patient appears to be an ultra-fast metabolizer due to a polymorphism in the CYP2D6 enzyme. Because of this genetic modification this patient is not treated with a standard dose of metoprolol. How will the dosage for this patient be adjusted?
A patient with a known brain tumor is brought to the emergency ward for status epilepticus. After failed attempts with other anti-epileptics, you decide to treat her with phenytoin. The seizure stops after the loading dose, and she is put on maintenance therapy. After some time, the blood pressure and respiratory rate of this patient decreases and she gets into a coma. This reaction is a serious side effect of phenytoin. Phenytoin is metabolized into inactive metabolites by CYP2C9 enzymes in the liver and you are considering that this patient may have a genetic mutation in the gene encoding for CYP2C9. What would be the most probable CYP2C9 phenotype of this patient?
