Influence of pyruvate on ammonia metabolism by renal cortical mitochondria.

Influence of pyruvate on ammonia metabolism by renal cortical mitochondria.
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丙酮酸对肾皮质线粒体氨代谢的影响。

DOI:
10.1038/ki.1982.166
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发表时间:
1982
影响因子:
19.6
通讯作者:
Kunin,AS
Kunin,AS
中科院分区:
医学1区
文献类型:
--
作者:
Tannen,RL;Kunin,AS

文献摘要

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丙酮酸对肾皮质线粒体氨代谢的影响。通过定量其关键氮和碳代谢物来评估三羧酸(TCA)循环前体丙酮酸对分离的肾皮质线粒体谷氨酰胺代谢的影响。当正常大鼠的线粒体在 pH 7.4 下孵育时,丙酮酸 (2 mM) 通过几乎完全消除谷氨酸脱氨作用和减少谷氨酰胺脱氨作用(但程度较小)来抑制氨的产生。培养介质中的 Alpha KG、柠檬酸盐和苹果酸盐积累显着增加,反映了通过 TCA 循环的丙酮酸通量的增加; Alpha KG 和谷氨酸的线粒体内浓度均增加。因此,丙酮酸主要抑制通过谷氨酸脱氢酶的通量,这是由于 Alpha KG 浓度增加和/或氧化还原 (NAD/NADH) 电位降低(继发于 TCA 循环通量增加)。谷氨酰胺脱酰胺作用其次受到抑制,可能是由于线粒体内谷氨酸浓度增加。柠檬酸盐 (2 mM) 产生的变化与丙酮酸盐观察到的变化相当。在 pH 7.0 下孵育的正常大鼠的线粒体以及患有慢性代谢性酸中毒的大鼠的线粒体对丙酮酸的反应方式与在 pH 7.4 下孵育的正常线粒体性质相似。谷氨酸脱氨基作用受到显着抑制,但尽管存在丙酮酸,但慢性酸中毒时谷氨酸脱氨基作用仍然很高。然而,当谷氨酰胺代谢与在 pH 7.4 下孵育的正常线粒体进行对比时,无论孵育介质中是否单独存在谷氨酰胺或与丙酮酸组合,对酸性 pH 下体外孵育以及慢性代谢性酸中毒的反应在数量上相似。丙酮酸对肾皮质线粒体氨代谢的影响。 L'effet du pyruvate, un precurseur du Cycle des Acides tricarboxyliques (TCA) sur Ic métaholisme de Ia glutamine par des mitochondries isolées de cortical rénale a été étudié en quantifiant ses principaux métabolites azotés etcarbonés.正常大鼠的线粒体在 pH 值 7、4 时,丙酮酸 (2 mM) 会抑制氨的产生,并补充谷氨酸的脱氨作用。谷氨酰胺的脱氨作用是通过一种不同的方法来实现的。 α乙酰戊二酸、柠檬酸和苹果酸在孵化环境中的积累需要考虑增强,丙酮酸通量的反射增强会穿过 TCA 循环;线粒体内α-脑戊二酸和谷氨酸浓度增加。由于丙酮酸抑制原始 Ic 通量 a 穿过谷氨酸脱氢酶,因此 cc 导致 Ia 浓度 d'α 戊二酸浓度增加,因此氧化还原电位 (NAD/NADH) 沙丘减少 (NAD/NADH) 二级 Ia 刺激 du 通量 a 穿过 Ic 循环 des
Influence of pyruvate on ammonia metabolism by renal cortical mitochondria. The effect of the tricarboxylic acid (TCA) cycle precursor, pyruvate, on glutamine metabolism by isolated renal cortical mitochondna was assessed by quantitating its key nitrogen and carbon metabolites. When mitochondria from normal rats were incubated at pH 7.4, pyruvate (2 mM) inhibited ammonia production by almost completely erradicating glutamate deamination and by diminishing glutamine deam-idation but to a lesser extent. Alpha KG, citrate, and malate accumulation in the incubation medium were increased dramatically reflecting the increased flux of pyruvate through the TCA cycle; the intramitochondrial concentrations of both Alpha KG and glutamate were in-creased. Thus, pyruvate primarily inhibits flux through glutamate dehydrogenase as a result either of an increase in Alpha KG concentration and/or a decrease in the redox (NAD/NADH) potential secondary to enhanced flux through the TCA cycle. Glutamine deamidation is secondarily inhibited, presumably due to the increased intramitochondrial concentration of glutamate. Citrate (2 mM) produced changes comparable to those observed with pyruvate. Mitochondria from normal rats incubated at pH 7.0 as well as mitochondria from rats with chronic metabolic acidosis responded to pyruvate in a fashion qualitatively similar to normal mitochondria incubated at pH 7.4. Glutamate deamination was inhibited significantly, but a high rate persisted with chronic acidosis despite the presence of pyruvate. Nevertheless, when glutamine metabolism was contrasted with normal mitochondria incu-bated at pH 7.4, the response to in vitro incubation in an acid pH as well as to chronic metabolic acidosis was similar quantitatively regardless of whether glutamine alone or in combination with pyruvate was present in the incubation medium.Influence du pyruvate sur le métabolisme de l'ammoniac par des mitochondries de cortex renal. L'effet du pyruvate, un précurseur du cycle des acides tricarboxyliques (TCA) sur Ic métaholisme de Ia glutamine par des mitochondries isolées de corticale rénale a été étudié en quantifiant ses principaux métabolites azotés et carbonés. Quand des mitochondries de rats normaux étaient incubées a pH 7, 4, Ic pyruvate (2 mM) inhibait Ia production d'ammoniac en supprimant presque cornpletement Ia désamination du glutamate. et en diminuant Ia désaminationde la glutamine dans une moindre mesure. L'accumulation d'alphacetoglutarate, de citrate, et de malate dans Ic milieu d'incubation était considérablement augmentée, reflétant l'augmentation du flux du pyru-vate a travers Ic cycle des TCA; les concentrations intramitochon-driales d'alpha cétoglutarate et de glutamate étaient augmentées. Ainsi Ic pyruvate inhibe primitivement Ic flux a travers La glutamate déshydrogénase, cc qui résulte soit dune augmentation de Ia concentration d'alpha cétoglutarate, soit (et) dune diminution du potentiel redox (NAD/NADH) secondaire a Ia stimulation du flux a travers Ic cycle des