Creator:
Date:
Abstract:
Oxidation is one of the major mechanisms leading to the bioactivation of toxicants [1]. Identification of the CYPs driving the oxidation could be used to identify the possibility of localized toxicity. This project identifies CYP 2A6 as a possible enzyme for the oxidation of 6:2 FTOH. The Michaelis Menten curve generated a KM and VMax of 4076.4 ± 581.9 ng/mL and 68.8 ± 2.8 ng/mL/min respectively. Once inhibited with tranylcypromine, HCl, the KM and VMax were determined to be 8796.2 ± 1366.1 ng/mL and 69.5 ± 4.1 ng/mL/min, representing competitive inhibition. We demonstrated that CYP 2A6 was responsible for 6:2 FTOH metabolism using human recombinant assays with purified CYP 2A6. These assays yielded a 6:2 FTOH metabolic conversion rate of 0.42 ng/mL/min. This rate significantly decreased with the addition of Tranylcypromine HCl. This confirms CYP 2A6 as an active enzyme for the metabolism of 6:2 FTOH in the human liver.