Cytochrome P-450

Aka: Cytochrome P-450, Cytochrome P450, CYP450, Cytochrome P450 Induction

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II. Background

  1. Cytochrome P450 is central to hepatic metabolism of medications
    1. Cytochrome P450 is named for its maximal light absorption wave length of 450 nm
    2. Hepatocytes in the liver contain a P450 family of microsomal enzymes on the endoplasmic reticulum
  2. Cytochrome P450 enzymes are responsible for 80% of drug-Drug Interactions
  3. Primary role of CYP enzymes is to facilitate drug excretion by increasing drug polarity and hence water solubility
    1. P450 Enzymes facilitate drug oxidation and reduction, utilizing NADPH donated electrons (Phase 1 Reaction)
  4. Cytochrome P450 enzymes may be induced to greater activity
    1. Certain drugs stimulate an increased production and activity of specific CYP450 isoenzymes
    2. Increased isoenzyme levels increase metabolism of both inducer drugs, AND other drugs metabolized by the same isoenzyme
    3. Examples: Alcohol, Carbamazepine, Phenytoin, St. John's Wort

III. Types: Cytochrome P-450 Isoenzymes

  1. Hepatic Isoenzymes
    1. CYP3As (40-60% hepatic P-450 isoenzymes)
    2. CYP2D6 (2-5% hepatic P-450 isoenzymes)
    3. CYP2As (<1% hepatic P-450 isoenzymes)
    4. CYP1A2
    5. CYP2Cs
  2. Other Isoenzymes
    1. CYP1A1
    2. CYP2Bs
    3. CYP2E1
    4. CYP4As

IV. References

  1. (1999) Med Lett Drugs Ther 41(1056): 61-2 [PubMed]
  2. Ament (2000) Am Fam Physician 61(6): 1745-54 [PubMed]
  3. Bhatia (1997) Am Fam Physician 55(5):1683-94 [PubMed]
  4. Flockhart (2002) Arch Intern Med 162:405-12 [PubMed]
  5. Johnson (1999) Postgrad Med 105(2):193-222 [PubMed]

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