Significance of NADH-vanadate-oxidoreductase of cardiac and erythrocyte cell membranes.
Vanadate(V), which has positive inotropic, natriuretic and vasoconstrictive effects, is taken up by cardiac cells and erythrocytes in large quantities. Most of the intracellular vanadium is shown to exist as protein-bound vanadyl(IV), however Vanadate (VO3) is a powerful inhibitor of the (Na+ rK+)-ATPase and the Ca++-ATPase, whereas it stimulates adenylate cyclase of cardiac tissue. Vanadyl (VO2+) has no or much less effects on these enzymes. Plasma membranes of cardiac tissue (cat, calf, human) as well as erythrocytes contain an enzyme that converts vanadate(V) to vanadyl(IV) in the presence of NADH but not NADPH. The optimal conditions for this NADH-vanadate-oxidoreductase are: pH 6.8, 1 mM, NADH, 1.5 mM Va3VO4. Mg++ inhibits the enzyme half-maximally at 3 mM, Ca++ stimulates at low and inhibits at high concentrations (half-maximally at 0.8 mM). The enzyme is supposed to be located at the inner side of the cell membrane. Vanadate has been proposed as an ideal regulator of active cation transport across the cell membrane. The finding of a HADH-vanadate-oxidoreductase converting vanadate into the rather inactive vanadyl further supports this hypotheses. The amount of vanadate at active sites of the target enzymes might be responsible for the known vanadate effects.
D000818:Animals; D002415:Cats; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D010088:Oxidoreductases / Q000302:isolation & purification* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014638:Vanadates; D014639:Vanadium / Q000378:metabolism* / Q000494:pharmacology
D014639:Vanadium; D009243:NAD; D014638:Vanadates; D010088:Oxidoreductases; C027960:NADH-vandate oxidoreductase; D000254:Sodium-Potassium-Exchanging ATPase