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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Influence of substrate activation (hydrolysis of ATP by first steps of glycolysis and beta-oxidation) on the effect of enzyme deficiencies, inhibitors, substrate shortage and energy demand on oxidative phosphorylation.
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Influence of substrate activation (hydrolysis of ATP by first steps of glycolysis and beta-oxidation) on the effect of enzyme deficiencies, inhibitors, substrate shortage and energy demand on oxidative phosphorylation.

机译:底物活化(通过糖酵解和β-氧化的第一步水解ATP)对酶缺乏,抑制剂,底物短缺和能量需求对氧化磷酸化的影响。

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摘要

In intact tissues respiratory substrates (glucose, fatty acids) must be activated with the use of ATP before they may be oxidised and used for energy (ATP) production. This activation by product constitutes an example of a typical positive feedback. In the present paper, the influence of substrate activation on the effect of inborn enzyme deficiencies, inhibitors, lowered oxygen tension, respiratory fuel shortage and increased energy demand on respiration and ATP synthesis is studied with the aid of the dynamic computer model of oxidative phosphorylation in isolated mitochondria developed previously. Computer simulations demonstrate that, in the case where oxidative phosphorylation in the whole organism is partially inhibited, the necessity of substrate activation can have significant impact on the relationship between the activity of (particular steps of) oxidative phosphorylation (or the value of energy demand) and the respiration rate. Depending on the sensitivity of ATP usage to ATP concentration, substrate activation may either slightly enhance the effect of the decrease in the oxidative phosphorylation activity (increase in energy demand) or may lead to a non-stability and sudden collapse of the respiration rate and phosphorylation potential below (above) a certain threshold value of oxidative phosphorylation activity (energy demand). This theoretical finding suggests a possible causal relationship between the affinity of ATP usage to [ATP] and the tissue specificity of mitochondrial diseases.
机译:在完整的组织中,必须先使用ATP激活呼吸底物(葡萄糖,脂肪酸),然后才能将其氧化并用于产生能量(ATP)。产品的这种激活构成了典型正反馈的一个例子。本文利用氧化磷酸化的动态计算机模型研究了底物活化对先天酶缺乏,抑制剂,降低的氧气张力,呼吸燃料短缺以及能量需求增加对呼吸和ATP合成的影响。孤立的线粒体以前发展。计算机模拟表明,在整个生物体内的氧化磷酸化被部分抑制的情况下,底物活化的必要性可能会对氧化磷酸化(特定步骤)的活性(或能量需求值)之间的关系产生重大影响。和呼吸频率。取决于ATP使用对ATP浓度的敏感性,底物激活可能会稍微增强氧化磷酸化活性降低的效果(增加能量需求),或者可能导致呼吸频率和磷酸化的不稳定和突然崩溃电势低于(高于)氧化磷酸化活性的一定阈值(能量需求)。这一理论发现表明,ATP使用对[ATP]的亲和力与线粒体疾病的组织特异性之间可能存在因果关系。

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