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Hepatic microsome


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Hepatic microsome

  1. 1. Hepatic microsome • The cytochrome P450 system is a group of enzymes that control the concentrations of many endogenous substances and drugs. These enzymes are mainly found in the liver (hepatic microsomal enzymes) and gut • Cytochrome P450 system is comprised of about 40- 50 isoenzymes. Each isoenzyme is derived from the expression of an individual gene. Originally the system was identified as a pigment in hepatic microsomes.
  2. 2. • . When examined, the pigment had a characteristic spectrophotometric profile with an associated peak at 450nm (hence the term cytochrome P450 system) .The main effect of the cytochrome P450 enzymes is to catalyse oxidation, which generally makes the substrate more water-soluble and so more readily excreted by the kidney. • There are many isoenzymes in the cytochrome P450 system, only a few appear to be responsible for the metabolism of commonly used drugs (CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A3, CYP 3A4)
  3. 3. The metabolism of drugs that are inactivated by the cytochrome P450 enzymes can be altered by substances which either induce these enzymes and therefore increase degradation, or substances that inhibit these enzymes and therefore are associated with increased levels of the drug CYP enzymes have been identified in all domains of life - animals, plants, fungi, protists, bacteria, archaea, and even in viruses
  4. 4. • The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into the aliphatic position of an organic substrate (RH) while the other oxygen atom is reduced to water: RH + O2 + NADPH + H+ → ROH + H2O + NADP. +Human CYPs are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize thousands of endogenous and exogenous chemicals.