title: β-Citryl-L-glutamate acts as an iron carrier to activate aconitase activity.
abstract: The compound β-citryl-L-glutamate (β-CG) was initially isolated from developing brains, though its functional roles remain unclear. In in vitro experiments, the [Fe(II)(β-CG)] complex activated aconitase in the presence of reducing reagents, whereas no Fe complex with citrate, glutamate, or deferoxamine displayed such an effect. β-CG and [Fe(II)(β-CG)] both bound to the fourth labile Fe atom (Fe(a)) in the [4Fe-4S] cluster of aconitase. Furthermore, [Fe(II)(β-CG)] reactivated aconitase damaged by ammonium peroxodisulfate (APS), while β-CG and citrate had no effect. These findings suggest that [Fe(II)(β-CG)] can transfer Fe to aconitase disassembled by APS. In intact mitochondria, both β-CG and [Fe(II)(β-CG)] bound to Fe(a) of aconitase, whereas only [Fe(II)(β-CG)] reactivated the enzyme disassembled by APS. In cultured neuronal cells, β-CG significantly enhanced cell viability by accelerating mitochondrial activity in primary cultures of neurons from newborn mouse cerebrum tissues. Thus, the β-CG plays a role as an Fe-carrier for mitochondrial aconitase, and then activates it. Taken together, these findings suggest that β-CG is an endogenous low molecular weight Fe chaperone for aconitase.
authors: Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
authors: Michiko
authors: M
authors: Hamada-Kanazawa
authors: Masanori
authors: M
authors: Narahara
authors: Masaoki
authors: M
authors: Takano
authors: Kyong Son
authors: KS
authors: Min
authors: Keiichi
authors: K
authors: Tanaka
authors: Masaharu
authors: M
authors: Miyake
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D051379:Mice; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism
chemical_list: C584236:(beta-citrylglutamate)iron(II); D005296:Ferrous Compounds; D005971:Glutamates; D007502:Iron Chelating Agents; C018491:beta-citrylglutamic acid; D004247:DNA; D007501:Iron; D000154:Aconitate Hydratase