CYP3A4: Difference between revisions

'''Cytochrome P450 3A4''' (CYP3A4) is in the heme-thiolate monooxygenase enzyme family meaning the protein contains a heme group with an iron atom.  Enzymes in [[Cytochrome P450]] are oxidizing enzymes and CYP3A4 works in the body oxidizing foreign molecules such as toxins and drugs<ref name="a">PMID:16389357</ref><ref name="b">PMID:15603755</ref>. It appears almost half of the marketed pharmaceutical drugs are metabolized by CYP3A4 [http://www.pharmacytimes.com/publications/issue/2008/2008-09/2008-09-8687] All Cytochrome P450 are essential enzymes for metabolism and the enzyme CYP3A4 is the most important. [http://www.medsafe.govt.nz/profs/PUArticles/March2014DrugMetabolismCytochromeP4503A4.htm] Primarily found in the liver and intestine, CYP3A4 is localized in the endoplasmic reticulum membrane [http://www.uniprot.org/uniprot/P08684] and are present in all eukaryotic organisms as well as some prokaryotes<ref name="c">PMID: 15352783</ref>. While CYP3A4's role in drug metabolism are numerous, they are often aiding deactivation through facilitated excretion from the system or by direct inactivation. [https://en.wikipedia.org/wiki/CYP3A4#Tissue_distribution]  

The <scene name='72/728174/N_to_c_terminus/1'>alpha helices</scene> can be seen colored in rainbow succession from the N to C terminus.  The protein pocket, where the reactions are catalyzed, more specifically, the <scene name='72/728174/Heme_binding_site/1'>heme binding site</scene> contains twenty-two residues [http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=4NY4] but the main interaction is with a Cysteine at position 442, which coordinates with iron. [http://www.uniprot.org/uniprot/P08684].  

== Drug Metabolism ==

CYP3A4 is thought to affect the metabolism of 30-60% of the drugs on the market [https://www.pharmgkb.org/gene/PA130?tabType=tabVip#tabview=tab3&subtab=32] [http://www.pharmacytimes.com/publications/issue/2008/2008-09/2008-09-8687].     An orally prescribed drug can take a while to arrive at its target cell and along the way the body has enzymes that filter out the drug dampening its efficacy.  Of those enzymes, CYP3A4 is a main player and still a lot more needs to be learned.  In many cases, like that of the ß2 receptor, there is only a fraction of the drug remaining after what is known as the first-pass metabolism so that by the time the drug gets to the circulatory system where it can be delivered to the tissues its potency has already been compromised <ref name="h"> PMCID: PMC2045626</ref>. 

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