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Why study the cytochrome P4503A (CYP3A) family?

Published on October 1, 2007 Reviewed on August 11, 2015   52 min

A selection of talks on Biochemistry

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0:00
Why study the Cytochrome P4503A family, also known as the CYP3As?
0:10
First, The CYP3A family is the most abundant CYP in human liver. When a bank of human livers was immuno-quantitated for the amounts of the major CYPs, CYP3A was found to represent on average about 30 percent of total hepatic P450, making it the dominant CYP in this tissue.
0:34
Secondly, not only is CYP3A the most abundant hepatic CYP, but a survey of drug reactions demonstrated that CYP3As catalyzed the metabolism of approximately 50 percent of all drugs in clinical use. Thus, based on these criteria, it could be argued that CYP3A is the most important CYP in human liver.
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The CYP3A family is comprised of four genes, which are all located in tandem on chromosome 7q21 to 22, and span about 230kb of DNA. The four CYP3A genes are CYP3A43, CYP3A4, CYP3A5, and CYP3A7. There are two pseudo genes located on the locus, CYP3AP1 and P2. It is believed the hierarchy of importance of CYP3A to metabolism is that 3A4 is the most important, followed by 3A5, and 3A7 in fetal liver.
1:39
CYP3A4 was first isolated and called HL5, then purified and called HLp or P450NF. Two groups cloned the first human CYP3AcDNA, CYP3A4, and CYP3A3. These cDNAs differed by only 14 nucleotides. However, amplification with primers revealed that only CYP3A4 is significantly expressed. Thus, original publications with any of this nomenclature are all referring to the same CYP, now called CYP3A4.
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Why study the cytochrome P4503A (CYP3A) family?

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