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. Author manuscript; available in PMC: 2017 Dec 27.
Published in final edited form as: Biochemistry. 2017 Dec 12;56(51):6700–6712. doi: 10.1021/acs.biochem.7b01025

Figure 8.

Figure 8

Summary DOX-mediated and 7-de-aDOX-mediated effects on AA metabolism by CYP2J2. (A) DOX-mediated effects. DOX binding from all data displays one-site, competitive inhibition of AA metabolism. When bound to the active site of CYP2J2, DOX occupies a majority of the volume and prevents AA from binding and being converted to EETs. 7-de-aDOX-mediated effects. DOX is reduced to 7-de-aDOX by CPR. 7-de-aDOX then binds into the active site of CYP2J2 into a pocket that directs AA binding. This positions AA with Carbons C5, C6, C8, and C9 closest to the heme. The result is an incomplete inhibition of AA metabolism with a larger percentage of 5,6-EET and a lower percentage of 14,15-EET in the total EETs present. (B) Summary of CYP2J2-mediated AA metabolism by all anthracyclines studied.