The pathway of adenine nucleotide catabolism and its control in isolated rat hepatocytes subjected to anoxia.
The pathway of adenine nucleotide catabolism and its control in isolated rat hepatocytes subjected to anoxia.
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缺氧大鼠离体肝细胞腺嘌呤核苷酸分解代谢途径及其控制。
DOI：
10.1042/bj2020117
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Hers,HG
中科院分区：
文献类型：
--
作者：
Vincent,MF;VandenBerghe,G;Hers,HG
1. 在离体大鼠肝细胞中研究了由 N2/CO2 取代 O2/CO2 气相引起的腺嘌呤核苷酸库的分解，目的是确定缺氧条件下 AMP 分解代谢的途径。 2. 大约。缺氧 40-60 分钟后，40% 的腺嘌呤核苷酸池丢失。在喂食大鼠的肝细胞中，ATP 缓慢消失。这可以通过糖原储存的存在来解释，糖原储存允许通过无氧糖酵解产生 ATP。在24小时饥饿大鼠的肝细胞中，ATP在5分钟内几乎完全消失，部分被AMP的积累所取代。这表明另一种机制在饥饿状态下保护腺嘌呤核苷酸库。在这两种情况下，腺嘌呤核苷酸的损失主要是由于尿酸氧化酶的氧依赖性而导致尿酸的积累。 3.在已知可选择性抑制腺苷脱氨酶的浓度下用考福霉素抑制O 2 之前孵育肝细胞不会导致腺苷积累，并且不会影响尿酸的形成。这表明在这些条件下，AMP 的降解不会通过 5'-核苷酸酶进行。然而，在抑制 AMP 脱氨酶浓度的辅福霉素存在下，尿酸的形成几乎被抑制，这表明 AMP 的初始降解是由后一种酶催化的。 4. 饥饿状态下AMP的积累可以通过ATP（AMP脱氨酶的主要刺激剂）的显着减少和Pi（其生理抑制剂之一）的增加来解释。这些效应子的修饰也可以解释饥饿大鼠肝细胞中细胞质 5'-核苷酸酶的抑制作用增强，这可以通过在没有考福霉素的情况下 IMP 的积累来证明。 5.缺氧20分钟后肝细胞的再氧合诱导ATP迅速再生，其浓度达到等于预先存在的AMP浓度。 6. 对于肝细胞与0.1μm-辅福霉素预孵育后观察到的IMP积累没有任何解释，因为IMP代谢酶的活性不受这种肌苷类似物的影响。
1. The breakdown of the adenine nucleotide pool provoked by the replacement of the O2/CO2gas phase by N2/CO2was studied in isolated rat hepatocytes with the purpose of defining the pathway of the catabolism of AMP in anoxic conditions. 2. Approx. 40% of the adenine nucleotide pool was lost after 40–60 min of anoxia. In hepatocytes from fed rats there was a slow disappearance of ATP. This is explained by the presence of glycogen stores, allowing the generation of ATP by anaerobic glycolysis. In hepatocytes from 24h-starved rats, ATP almost completely disappeared within 5 min, and was partly replaced by an accumulation of AMP. This indicates that another mechanism protects the adenine nucleotide pool in the starved state. In both conditions, the loss of adenine nucleotides was mainly accounted for by an accumulation of uric acid, owing to the oxygen-dependence of urate oxidase. 3. Incubation of the hepatocytes before the suppression of O2with coformycin at concentrations known to inhibit selectively adenosine deaminase did not result in an accumulation of adenosine and did not influence the formation of uric acid. This indicates that the degradation of AMP does not proceed by way of 5′-nucleotidase under these conditions. In the presence of coformycin at concentrations which are inhibitory to AMP deaminase, however, the formation of uric acid was nearly suppressed, demonstrating that the initial degradation of AMP was catalysed by the latter enzyme. 4. The accumulation of AMP in the starved state can be explained by the pronounced decrease in ATP, the major stimulator of AMP deaminase, and the enhanced increase in Pi, one of its physiological inhibitors. The modifications of these effectors can also explain the increased inhibition of the cytoplasmic 5′-nucleotidase, shown by the accumulation of IMP in the absence of coformycin, in hepatocytes from starved rats. 5. Reoxygenation of the hepatocytes after 20 min of anoxia induced a prompt regeneration of ATP, which reached concentrations equal to the pre-existing concentration of AMP. 6. No explanation was found for the accumulation of IMP observed after preincubation of the hepatocytes with 0.1μm-coformycin, since the activities of the IMP-metabolizing enzymes were not influenced by this inosine analogue.