Effects of aluminum on activity of krebs cycle enzymes and glutamate dehydrogenase in rat brain homogenate.
Aluminum is a neurotoxic agent for animals and humans that has been implicated as an etiological factor in several neurodegenerative diseases and as a destabilizer of cell membranes. Due to its high reactivity, Al3+ is able to interfere with several biological functions, including enzymatic activities in key metabolic pathways. In this paper we report that, among the enzymes that constitute the Krebs cycle, only two are activated by aluminum: alpha-ketoglutarate dehydrogenase and succinate dehydrogenase. In contrast, aconitase, shows decreased activity in the presence of the metal ion. Al3+ also inhibits glutamate dehydrogenase, an allosteric enzyme that is closely linked to the Krebs cycle. A possible correlation between aluminum, the Krebs cycle and aging processes is discussed.
Zatta
P
P
CNR Center on Metalloproteins, and Department of Pharmacological Sciences, University of Padova, Italy. zatta@cribi1.bio.unipd.it
Lain
E
E
Cagnolini
C
C
D000154:Aconitate Hydratase / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002952:Citric Acid Cycle / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000535:Aluminum; D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D000154:Aconitate Hydratase