Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione

Abstract

Triketone herbicides are inhibitors of 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key enzyme of the tyrosine transformation pathway, common for plants and animals. One of these herbicides, 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), is so selective and efficient that it can be applied as a medicine in a hereditary metabolic disease - tyrosinemia type I. In this paper the available information concerning the molecular mechanism of HPPD inhibition by NTBC, originating from experimental investigations as well as theoretical modeling, has been collected. It is supplemented by results of additional theoretical DFT and/or MP2 calculations of the energetic effects of individual elementary molecular transformations. All these data are discussed and a consistent picture of HPPD inhibition by NTBC is proposed.