“…Given that the xanthine oxidase reaction involves obligatory two-electron chemistry, 132 and that the enzyme is known to catalyze the dehydroxylation of uric acid to xanthine under strongly reducing conditions, 260 the possibility cannot be excluded that the 4-hydroxybenzoyl-CoA dehydrogenase reaction in fact runs simply in the reverse of the hydroxylation pathway for xanthine oxidase, with hydride transfer from an equatorial Mo-SH to C-4 of molybdenum-coordinated substrate, followed directly by dehydroxylation and rearomatization. It has been proposed, however, that the enzyme operates via a radical-based Birch-like mechanism, 259 in which a first reducing equivalent is added to molybdenum-coordinated substrate, followed by protonation at C-4 of substrate and addition of a second reducing equivalent, which leads to dehydroxylation and rearomatization.…”