Differential effects of monovalent, divalent and trivalent metal ions on rat brain hexokinase.
The effects of monovalent (Li+, Cs+) divalent (Cu2+, Ca2+, Sr2+, Ba2+, Zn2+, Cd2+, Hg2+, Pb2+, Mn2+, Fe2+, Co2+, Ni2+) and trivalent (Cr3+, Fe3+, Al3+) metals ions on hexokinase activity in rat brain cytosol were compared at 500 microM. The rank order of their potency as inhibitors of brain hexokinase was: Cr3+ (IC50 = 1.3 microM) greater than Hg2+ = Al3+ greater than Cu2+ greater than Pb2+ (IC50 = 80 microM) greater than Fe3+ (IC50 = 250 microM) greater than Cd2+ (IC50 = 540 microM) greater than Zn2+ (IC50 = 560 microM). However, at 500 microM Co2+ slightly stimulated brain hexokinase whereas the other metal ions were without effect. That inhibition of brain glucose metabolism may be an important mechanism in the neurotoxicity of metals is suggested.
Lai
J C
JC
Baker
A
A
Carlson
K C
KC
Blass
J P
JP
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D004789:Enzyme Activation / Q000187:drug effects; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D051381:Rats
D002413:Cations, Divalent; D002414:Cations, Monovalent; D008670:Metals; D006593:Hexokinase