Influence of pyruvate on ammonia metabolism by renal cortical mitochondria.
Influence of pyruvate on ammonia metabolism by renal cortical mitochondria.
复制标题
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
中科院分区:
文献类型:
--
作者:
Tannen,RL;Kunin,AS
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