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Kynurenines and the respiratory parameters on rat heart mitochondria.

机译:动力学尿素和大鼠心脏线粒体的呼吸参数。

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It has been shown recently that the L-kynurenine metabolite kynurenic acid lowers the efficacy of mitochondria ATP synthesis by significantly increasing state IV, and reducing respiratory control index and ADP/oxygen ratio of glutamate/malate-consuming heart mitochondria. In the present study we investigated the effect of L-tryptophan (1.25 microM to 5 mM) and other metabolites of L-kynurenine as 3-hydroxykynurenine (1.25 microM to 2.5 mM), anthranilic acid (1.25 microM to 5 mM) and 3-hydroxyanthranilic acid (1.25 microM to 5 mM) on the heart mitochondria function. Mitochondria were incubated with saturating concentrations of respiratory substrates glutamate/malate (5 mM), succinate (10 mM) or NADH (1 mM) in the presence or absence of L-tryptophan metabolites. Among tested substances, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and anthranilic acid but not tryptophan affected the respiratory parameters dose-dependently, however at a high concentration, of a micro molar range. 3-Hydroxykynurenine and3-hydroxyanthranilic acid lowered respiratory control index and ADP/oxygen ratio in the presence of glutamate/malate and succinate but not with NADH. While, anthranilic acid reduced state III oxygen consumption rate and lowered the respiratory control index only of glutamate/malate-consuming heart mitochondria. Co-application of anthranilic acid and kynurenic acid (125 or 625 microM each) to glutamate/malate-consuming heart mitochondria caused a non-additive deterioration of the respiratory parameters determined predominantly by kynurenic acid. Accumulated data indicate that within L-tryptophan metabolites kynurenic acid is the most effective, followed by anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid to influence the respiratory parameters of heart mitochondria. Present data allow to speculate that changes of kynurenic acid and/or anthranilic acid formation in heart tissue mitochondria due to fluctuation of L-kynurenine metabolism may be of functional importance for cardiovascular processes. On the other hand, beside the effect of 3-hydroxyanthranilic acid and 3-hydroxykynurenine on respiratory parameters, their oxidative reactivity may contribute to impairment of mitochondria function, too.
机译:最近显示,L-犬尿氨酸代谢产物犬尿酸通过显着增加IV状态并降低呼吸控制指数和谷氨酸/苹果酸消耗性心脏线粒体的氧控制比,降低了线粒体ATP合成的功效。在本研究中,我们研究了L-色氨酸(1.25 microM至5 mM)和L-犬尿氨酸其他代谢产物的作用,如3-hydroxykynurenine(1.25 microM至2.5 mM),邻氨基苯甲酸(1.25 microM至5 mM)和3-羟基邻氨基苯甲酸(1.25 microM至5 mM)对心脏线粒体功能的影响。在存在或不存在L-色氨酸代谢产物的情况下,将线粒体与饱和浓度的呼吸道底物谷氨酸/苹果酸(5 mM),琥珀酸(10 mM)或NADH(1 mM)一起孵育。在被测物质中,3-羟基犬尿氨酸,3-羟基邻氨基苯甲酸和邻氨基苯甲酸而不是色氨酸影响呼吸参数,但是在微摩尔范围内浓度较高时,剂量依赖性。在谷氨酸/苹果酸和琥珀酸存在的情况下,3-羟基犬尿氨酸和3-羟基邻氨基苯甲酸降低了呼吸控制指数和ADP /氧气比,但没有NADH。同时,邻氨基苯甲酸仅降低谷氨酸/苹果酸消耗的心脏线粒体的III态耗氧率并降低呼吸控制指数。将邻氨基苯甲酸和强尿酸(每种分别为125或625 microM)联合应用到消耗谷氨酸/苹果酸的心脏线粒体中,会导致主要由强尿酸决定的呼吸参数的非累加性恶化。积累的数据表明,在L-色氨酸代谢产物中,犬尿酸是最有效的,其次是邻氨基苯甲酸,3-羟基犬尿氨酸,3-羟基邻氨基苯甲酸影响心脏线粒体的呼吸参数。目前的数据可以推测,由于L-犬尿氨酸代谢的波动,心脏组织线粒体中尿嘧啶酸和/或邻氨基苯甲酸形成的变化可能对心血管过程具有重要的功能。另一方面,除了3-羟基邻氨基苯甲酸和3-羟基犬尿氨酸对呼吸参数的影响外,它们的氧化反应性也可能导致线粒体功能受损。

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