Mechanism of Metabolic Ring Opening of Benzene and its Relation to Mammalian PAH Metabolism

Abstract

Benzene exhibits a metabolic dichotomy in that it is ring-opened by bacteria, via dioxygenases, to yield Z,Z-muconic acid which eventually is metabolized in the tricarboxylic acid cycle, while mammals produce the E,E-isomer, via monooxygenases, as a relatively minor product relative to phenol and other monocyclic species. The dichotomy is further evidenced by the ability of bacteria to metabolically ring open PAH while mammals appear to retain the fully cyclic structures. This dichotomy is explicable in terms of the postulated formation of 2,3-epoxyoxepin via two successive monooxygenations of benzene and oxepin. The absence (or rarity) of natural oxepin metabolites of PAH explains the absence of ring-opening metabolism in species dependent upon monooxygenases.

Key Words:

• 2,3-Epoxyoxepins
• PAH Metabolism
• Dialdehydes