β-Citryl-L-glutamate acts as an iron carrier to activate aconitase activity
| Autor: | Masaharu Miyake, Masaoki Takano, Keiichi Tanaka, Michiko Hamada-Kanazawa, Masanori Narahara, Kyong Son Min |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Iron
Pharmaceutical Science Chick Embryo Mitochondrion Iron Chelating Agents Aconitase Mitochondria Heart Mice Glutamates medicine Animals Viability assay Ferrous Compounds Cells Cultured Pharmacology chemistry.chemical_classification Aconitate Hydratase biology Glutamate receptor Brain General Medicine DNA In vitro Deferoxamine Enzyme Activation Enzyme Biochemistry chemistry Chaperone (protein) biology.protein medicine.drug |
| Zdroj: | Biologicalpharmaceutical bulletin. 34(9) |
| ISSN: | 1347-5215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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