Revealing metabolic path of Ketamine catalyzed by CYP450 via quantum mechanical approach

Ketamine is essential medication used in anesthesia. This drug is metabolized by CYP450 enzyme, found in human liver. After metabolism they form product called metabolites. It takes more time or less time to forming the product. So it is essential to investigate the mechanism of reaction, duration of reaction and side effects of formed metabolite. A reaction involves reactant complex, transition state, intermediate state and product. The present work concluded the barrier energies of these complexes that reveals the metabolic path of Ketamine via aliphatic hydroxylation step catalyzed by CYP450 enzyme. In current study, theoretical methods are utilized to investigate the mechanism, involved energetics, electronic reorganizations, structural information, barrier heights and Density Functional Theory (DFT) descriptors of the reactant & product, during the course of the reaction to elucidate the formation of product. The reaction is performed on two spin surfaces one is doublet another is quartet. It is concluded barrier height of transition states (TS) with single imaginary frequency (i1549.92 cm(-1) and i1205.31 cm(-1)) for doublet (16.07 kcal/mol) and quartet (16.61 kcal/mol) spin states, respectively. The present study is very much successful to understand the metabolic path of ketamine due to reliability and accuracy of results. These results will be very helpful for experimentalist to finding the transition state of reaction and theoretical researchers in filed of drug discovery to finding new drugs. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Ketamine, a crucial anesthesia medication, is metabolized by the CYP450 enzyme in the liver, forming metabolites. This study investigates the mechanism, energetics, and structural information of the metabolic pathway of ketamine using theoretical methods. The results provide important insights into the reaction mechanism and could aid experimentalists in finding transition states and theoretical researchers in drug discovery.