One-Electron Reduction of Vanadium(V) by Flavoenzymes/NADPH

It has been known for more than a decade that vanadium (V) stimulates the oxidation of NADH by plasma membranes (1) but the underlying mechanism is still not fully understood. This effect has been attributed to a membrane-associated NADH-dependent vanadium (V) oxidoreductase (1). Subsequent studies suggest that vanadium ( V) can accept an electron from fiavoprotein dehydrogenase that oxidizes NADH (2). The phenomenon ofNAD(P)H oxidation coupled to vanadium(V) reduction has also been demonstrated in other biological systems (3-6). A recent electron spin resonance (ESR) study from our laboratory reported on the accumulation of vanadium (IV) duringthe reduction ofvanadate (vanadium(V)) by the ftavoenzymes glutathione reductase (GSSG-R),4 lipoyl dehydrogenase, and ferredoxin-NADP+ oxidoreductase in the presence of NAD(P)H (7). It was concluded therein (7) that these ftavoenzymes function as NAD(P)H-dependent vanadium(V) reductases. More recently, however, Liochev and Fridovich (8) have argued that the ESR data (7) do not demonstrate that the investigated fiavoenzymes act as vanadate reductases. They suggest an alternative mechanism in which the fiavoenzyme simply serves as a generator ofsuperoxide (02) radical, which acts as a propagator of the radical chain reaction leading to NAD(P)H oxidation (9, 10), as summarized below: