Silva C G, Silva A R, Ruschel C, Helegda C, Wyse A T, Wannmacher C M, Dutra-Filho C S, Wajner M
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Metab Brain Dis. 2000 Jun;15(2):123-31. doi: 10.1007/BF02679979.
The present study investigated the effects of glutaric acid (GA), which predominantly accumulates in glutaric acidemia type I (GA-I), on some in vitro parameters of energy metabolism in cerebral cortex of rats. We first evaluated CO2 production from [U-14C] acetate, as well as ATP levels in brain of young Wistar rats. The effect of the acid on the activities of the respiratory chain complexes were also investigated. GA was tested at final concentrations ranging from 0.5 to 5.0 mM. GA significantly reduced brain CO2 production by 50% at the concentrations of 0.5 to 3.0 mM, ATP levels by 25% at the concentration of 3.0 mM, succinate:cytochrome C oxireductase (complex II plus CoQ plus complex III) by 25% at 5 mM concentration, and NADH:cytochrome C oxireductase (complex I plus CoQ plus complex Ill) by 25% at 2.5 and 5 mM concentrations. The results strongly indicate that GA impairs brain energy production. If these effects also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by GA-I.
本研究调查了主要在I型戊二酸血症（GA-I）中蓄积的戊二酸（GA）对大鼠大脑皮质能量代谢的一些体外参数的影响。我们首先评估了[U-14C]乙酸盐产生的二氧化碳以及幼年Wistar大鼠大脑中的ATP水平。还研究了该酸对呼吸链复合物活性的影响。GA的测试终浓度范围为0.5至5.0 mM。在0.5至3.0 mM浓度下，GA使大脑二氧化碳产生量显著降低50%；在3.0 mM浓度下，ATP水平降低25%；在5 mM浓度下，琥珀酸：细胞色素C氧化还原酶（复合物II加辅酶Q加复合物III）降低25%；在2.5和5 mM浓度下，NADH：细胞色素C氧化还原酶（复合物I加辅酶Q加复合物III）降低25%。结果强烈表明GA损害大脑能量产生。如果这些影响也发生在人类身上，那么它们可能会导致受GA-I影响患者的神经病理学改变。
