ABSTRACT
Among those enzymes capable of carrying out the hydroxylation of either aliphatic or aromatic substrates, the molybdenum hydroxylases possess a unique reaction stoichiometry. Unlike systems utilizing heme, flavin or biopterin cofactors, the molybdenum enzymes use water as the source of oxygen to be incorporated into substrate rather than molecular oxygen. In the former cases the thermodynamic favorability of the overall reaction that is derived from the reduction of one of the atoms of dioxygen to water (utilizing external reducing equivalents, generally in the form of NAD(P)H) is used to generate a highly activated intermediate in the reaction cycle: a Fe(IV) = O in the case of the heme systems, 4a peroxides in the flavin (see Müller, Vol. I of this series), and biopterin systems. By contrast, the thermodynamic driving force for the molybdenum-catalyzed reactions is derived entirely from the oxidation of substrate itself and there is at present no evidence for an activated intermediate of the type encountered in the other systems. Thus, it is clear that the molybdenum hydroxylases represent a unique solution to the general problem of oxygen activation in biology. This review concerns itself with those complex molybdoflavoproteins catalyzing the hydroxylation of xanthine and related heterocycles as well as a variety of aldehydes. In addition to those aspects of protein function relevant to the flavin centers of the enzymes, the structure and function of the molybdenum center are also discussed. An effort has been made in the present review to provide on the one hand an appreciation of the extensive body of work dealing with the physicochemical properties of the enzymes, and at the same time give a critical overview of much of the exciting work that has taken place in the past 5 years. The reader is referred to other recent reviews for different perspectives of the field. 12
