Superoxide-Independent Reduction of Vanadate by Rat Liver Microsomes/NAD(P)H: Vanadate Reductase Activity

While it is known that vanadate and related compounds of pentavalent vanadium ( V (V)) exert potent toxic effects on a wide variety of biological systems, the underlying biochemical mechanism is still not fully understood ( 1- 3). One of the pathways is thought to involve the oxidation of NAD ( P) H. Thus, considerable effort has been devoted to finding the mechanism of NAD ( P) H oxidation by Vcvi (1-15). Erdmann et al. (5) first noted that vanadate stimulated the oxidation of NADH by plasma membranes and attributed this effect to a membrane containing NAD(P)H-dependent V(V) reductase. Later studies by Liochev and Fridovich indicated that endogenous superoxide ( 02 ) plays a central role in this reaction ( 4, 12, 13) . They proposed that NAD ( P) H dehydrogenases or oxidases produce 02, which causes VCV ) to stimulate NAD ( P) H oxidation via the following free radical chain mechanism ( 4, 12, 13) :