Inactivation of glucose-6-phosphate dehydrogenase isozymes from human and pig brain by aluminum.
Prolonged intake of low levels of aluminum from the drinking water has been found to increase the aluminum content in rat brain homogenates and to reduce the activity of hexokinase and glucose-6-phosphate dehydrogenase (G6PD). To determine the interaction of G6PD with aluminum in the brain, we have recently purified two isozymes of G6PD (isozymes I and II) from human and pig brain. Unlike isozyme I, isozyme II also had 6-phosphogluconate dehydrogenase (6-PGD) activity. We report here that G6PD isozymes I and II from human and pig brain purified to apparent homogeneity are inactivated by aluminum. Aluminum did not affect the 6-PGD activity of isozyme II. The aluminum-inactivated enzyme contained 1 mol of aluminum/mol of enzyme subunit. The protein-bound metal ion was not dissociated by exhaustive dialysis at 4 degrees C against 10 mM Tris-HCl (pH 7.0) containing 0.2 mM EDTA. Preincubation of aluminum with citrate, NADP+, EDTA, NaF, ATP, and apotransferrin protected the G6PD isozymes against aluminum inactivation. However, when the G6PD isozymes were completely inactivated by aluminum, only citrate, NaF, and apotransferrin restored the enzyme activity. The dissociation constants for the enzyme-aluminum complex of the isozymes varied from 2 to 4 microM, as measured by using NaF, a known chelator for aluminum. Inhibition of G6PD by low levels of aluminum further strengthens the suggested role of aluminum toxicity in the energy metabolism of the brain.
Cho
S W
SW
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Joshi
J G
JG
D000535:Aluminum / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002614:Chelating Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D013552:Swine
D002614:Chelating Agents; D007527:Isoenzymes; D000535:Aluminum; D005954:Glucosephosphate Dehydrogenase