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CYP2 family

Published on October 1, 2007 Updated on July 27, 2016   42 min

A selection of talks on Pharmaceutical Sciences

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0:00
Hello. I'm Ann Daly. And in the next 50 minutes or so I'm going to introduce you to the CYP2 cytochrome P450 family and its role in drug metabolism.
0:13
In terms of number of members, CYP2 is the largest human cytochrome P450 family, with about 30% of all human isoforms found here. There are over 20 different subfamilies in CYP2. But I'm going to concentrate on the main subfamilies that contribute to drug metabolism here. As shown, there are five of these subfamilies, CYP2A, CYP2B, CYP2C, CYP2D, and CYP2E. Each of these contain between one and three drug metabolizing isoforms. Other important CYP2 subfamilies include CYP2S and CYP2J. But I'm not going to consider these further as they mainly metabolize endogenous compounds rather than drugs and other xenobiologics.
1:11
The genes that encode members of the CYP2 family are all made up of nine exons, with each of these exons coding for part of the mature enzyme. Each isoform is the product of an entirely separate gene. But all the genes show a lot of homology. The homology between different subfamilies, such as CYP2A and CYP2B, is between 40% and 55% at the protein level. But two isoforms from the same family show homology of more than 55% at protein level. Different subfamilies are all derived from a common ancestor but in the course of evolution have generally migrated to different chromosomal locations. If we concentrate on the drug metabolizing subfamilies, CYP2A and CYP2B are found close to each other on chromosome 19. CYP2C and CYP2E are both found on chromosome 10 but at different locations. And CYP2D is found on chromosome 22. Where there is more than one isoform in the same subfamily, these genes will be side by side on the same chromosome.