β-Citryl-L-glutamate Acts as an Iron Carrier to Activate Aconitase Activity
β-Citryl-L-glutamate Acts as an Iron Carrier to Activate Aconitase Activity
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DOI：
10.1248/bpb.34.1455
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发表时间：
2011-09-01
影响因子：
2
通讯作者：
Miyake, Masaharu
中科院分区：
文献类型：
--
作者：
Hamada-Kanazawa, Michiko;Narahara, Masanori;Miyake, Masaharu
化合物beta-citryl-L-glutamate（beta-CG）最初是从发育中的大脑中分离出来的，尽管其功能作用仍不清楚。在体外实验中，[Fe（II）（β-CG）]复合物在还原剂的存在下激活顺乌头酸酶，而没有Fe复合物与柠檬酸盐，谷氨酸盐，或去铁胺显示这样的效果。β-CG和[Fe（II）（β-CG）]均与乌头酸酶[4Fe-4S]簇中的第四个不稳定Fe原子（Fe-a）结合。此外，[Fe（II）（beta-CG）]重新激活过硫酸铵（APS）损伤的乌头酸酶，而beta-CG和柠檬酸盐没有影响。这些结果表明，[Fe（II）（beta-CG）]可以将Fe转移到APS分解的乌头酸酶。在完整的线粒体中，β-CG和[Fe（II）（β-CG）]都与乌头酸酶的Fe-α结合，而只有[Fe（II）（β-CG）]重新激活被APS分解的酶。在培养的神经元细胞中，β-CG通过加速来自新生小鼠大脑组织的神经元原代培养物中的线粒体活性而显著增强细胞活力。因此，β-CG作为铁载体的线粒体顺乌头酸酶，然后激活它的作用。综上所述，这些研究结果表明，β-CG是内源性的低分子量铁伴侣的顺乌头酸酶。
The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, though its functional roles remain unclear. In in vitro experiments, the [Fe(II)(beta-CG)] complex activated aconitase in the presence of reducing reagents, whereas no Fe complex with citrate, glutamate, or deferoxamine displayed such an effect. beta-CG and [Fe(II)(beta-CG)] both bound to the fourth labile Fe atom (Fe-a) in the [4Fe-4S] cluster of aconitase. Furthermore, [Fe(II)(beta-CG)] reactivated aconitase damaged by ammonium peroxodisulfate (APS), while beta-CG and citrate had no effect. These findings suggest that [Fe(II)(beta-CG)] can transfer Fe to aconitase disassembled by APS. In intact mitochondria, both beta-CG and [Fe(II)(beta-CG)] bound to Fe-a of aconitase, whereas only [Fe(II)(beta-CG)] reactivated the enzyme disassembled by APS. In cultured neuronal cells, beta-CG significantly enhanced cell viability by accelerating mitochondrial activity in primary cultures of neurons from newborn mouse cerebrum tissues. Thus, the beta-CG plays a role as an Fe-carrier for mitochondrial aconitase, and then activates it. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chaperone for aconitase.