26 by: Robert Fischer

Student – Robert Fisher

Enzyme – Cytochrome P450 (232-387-9)

The enzyme is found on the ER. However, breakdown occurs in the liver, intestines, and kidneys but predominantly in the liver.

Cytochrome P450 (CYP) belongs to a super family of enzymes which play a significant role in metabolism, bioactivation, and the breakdown of xenobiotics (drugs) in humans. The main function of CYP in pharmacokinetics is converting drugs into soluble materials so they can be used by the body and excreted. CYP’s active site has a heme-iron-center which is bound to a protein by a cysteine thiolate molecule. Substrates can bind which induces a conformational change. From here, reductases transfer an electron from NAD(P)H followed by oxygen binding. A second electron is added via reduction creating an Fe-O2 group. This group gets protonated twice which releases water leaving behind Fe-OH. The drug can then take the -OH group increasing solubility and leave behind the original enzyme.

Fun fact: There are 57 isozymes discovered so far and 6 of them account for 90% of all drug metabolism.

References:

Guengerich, F.P.; Tateishi, Y.; McCarty, K.D.; Yoshimoto, F.K. Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations. Int. J. Mol.Sci. 2024, 25, 9020. https:// doi.org/10.3390/ijms25169020

Nelson, D. The Cytochrome P450 Homepage. Genome Databases. August 2009. Vol. 4, No. 1, (59-65).