Vanadate dimer and tetramer both inhibit glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides.
Vanadate dimer and tetramer inhibit glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. The inhibition by a vanadate mixture containing vanadate monomer, dimer, tetramer, and pentamer was determined by measuring the rates of glucose 6-phosphate oxidation and reduction of NAD (or NADP) catalyzed by glucose-6-phosphate dehydrogenase. The inhibition by vanadate is competitive with respect to NAD or NADP and noncompetitive (a mixed type) with respect to glucose 6-phosphate (G6P) when NAD or NADP are cofactors. This inhibition pattern varies from that observed with phosphate and thus suggests vanadate interacts differently than a phosphate analogue with the enzyme. 51V NMR spectroscopy was used to directly correlate the inhibition of vanadate solutions to the vanadate dimer and/or tetramer, respectively. The activity of the vanadate oligomer varied depending on the cofactor and which substrate was being varied. The vanadate dimer was the major inhibiting species with respect to NADP. This is in contrast to the vanadate tetramer, which was the major inhibiting species with respect to G6P and with respect to NAD. The inhibition by vanadate when G6P was varied was weak. The competitive inhibition pattern with respect to NAD and NADP suggests the possibility that vanadate oligomers may also inhibit catalysis of other NAD- or NADP-requiring dehydrogenases. Significant concentrations of vanadate dimer and tetramer are only found at fairly high vanadate concentrations, so these species are not likely to represent vanadium species present under normal physiological conditions. It is however possible the vanadate dimer and/or tetramer represent toxic vanadate species.
Crans
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Department of Chemistry, Colorado State University, Fort Collins 80523.
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D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D005958:Glucosephosphates / Q000378:metabolism; D007700:Kinetics; D007934:Leuconostoc / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D014638:Vanadates / Q000494:pharmacology*
D001426:Bacterial Proteins; D005958:Glucosephosphates; D009243:NAD; D014638:Vanadates; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase