Aluminum decreases the glutathione regeneration by the inhibition of NADP-isocitrate dehydrogenase in mitochondria.
Effect of aluminum on the NADPH supply and glutathione regeneration in mitochondria was analyzed. Reduced glutathione acted as a principal scavenger of reactive oxygen species in mitochondria. Aluminum inhibited the regeneration of glutathione from the oxidized form, and the effect was due to the inhibition of NADP-isocitrate dehydrogenase the only enzyme supplying NADPH in mitochondria. In cytosol, aluminum inhibited the glutathione regeneration dependent on NADPH supply by malic enzyme and NADP-isocitrate dehydrogenase, but did not affect the glucose 6-phosphate dehydrogenase dependent glutathione formation. Aluminum can cause oxidative damage on cellular biological processes by inhibiting glutathione regeneration through the inhibition of NADPH supply in mitochondria, but only a little inhibitory effect on the glutathione generation in cytosol.
Murakami
Keiko
K
Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Yoshino
Masataka
M
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008291:Malate Dehydrogenase / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction
D007523:Isocitrates; D009249:NADP; C034219:isocitric acid; D000535:Aluminum; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D007521:Isocitrate Dehydrogenase; D005979:Glutathione Peroxidase; D005978:Glutathione