Saakian G G, Saakian I R
Biomed Khim. 2008 Nov-Dec;54(6):696-705.
A high sensitivity of the succinate-dependent uptake of Ca2+ by mitochondria to (1) the transamination (TA) substrates glutamate (GLU) and alpha-ketoglutarate (KGL) and (2) the inhibitor of TA aminooxyacetate (AOA) was revealed. The effect of the TA substrates on Ca2+ uptake depends on the ratio (1:10 mM) of their concentrations: 1 mM GLU activates and 10 mM KGL decreases this activation by 35-46%, whereas AOA suppresses the Ca2+ capacity by 60% and the inhibitor of succinate oxidation malonate, by 80-90%. A similarity in the limiting action of KGL and phosphoenolpyruvate (PEP), two sources of oxaloacetate (OAA) and GTP, on Ca2+ capacity was revealed. The differences in the effects of KGL and GLU and the similarity in the effects of KGL and PEP on succinate oxidation are explained by the effect of OAA and GTP on this oxidation. The alternating inflow of OAA in coupled processes of TA, pyruvate cycle, and tricarboxylic acids cycle provides the reciprocal activation and cyclic recurrence of Ca2+ uptake, i. e., protection from the chronic exhausting activation of Ca2+-regulated dehydrogenases, the overload of Ca2+-outgoing channels, and the excessive production of free radicals in mitochondria. The reciprocal regulation of Ca2+ uptake by TA is considered as a mechanism of the maintenance of Ca2+ homeostasis and protection of mitochondria against Ca2+ overload.
线粒体对琥珀酸依赖性Ca2+摄取对（1）转氨基（TA）底物谷氨酸（GLU）和α-酮戊二酸（KGL）以及（2）TA抑制剂氨基氧乙酸（AOA）具有高敏感性。TA底物对Ca2+摄取的影响取决于它们浓度的比例（1:10 mM）：1 mM GLU激活，而10 mM KGL使这种激活降低35 - 46%，而AOA使Ca2+摄取能力降低60%，琥珀酸氧化抑制剂丙二酸使Ca2+摄取能力降低80 - 90%。揭示了草酰乙酸（OAA）和GTP的两种来源KGL和磷酸烯醇丙酮酸（PEP）对Ca2+摄取能力的限制作用具有相似性。KGL和GLU作用的差异以及KGL和PEP对琥珀酸氧化作用效果的相似性是由OAA和GTP对这种氧化的作用来解释的。在TA、丙酮酸循环和三羧酸循环的偶联过程中OAA的交替流入提供了Ca2+摄取的相互激活和循环重复，即保护免受Ca2+调节的脱氢酶的慢性耗竭性激活、Ca2+外流通道的过载以及线粒体中自由基的过量产生。TA对Ca2+摄取的相互调节被认为是维持Ca2+稳态和保护线粒体免受Ca2+过载的一种机制。
