Oxidative phosphorylation system during steady-state hypoxia in the dog brain.
Oxidative phosphorylation system during steady-state hypoxia in the dog brain.
复制标题
狗脑稳态缺氧期间的氧化磷酸化系统。
DOI：
10.1152/jappl.1990.68.6.2527
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Katzenberg,M
中科院分区：
文献类型：
--
作者：
Nioka,S;Smith,DS;Chance,B;Subramanian,HV;Butler,S;Katzenberg,M
用31 P核磁共振（NMR）技术研究了在体犬脑缺氧时生理生化反应与组织氧含量的关系。我们的研究结果表明，在缺氧过程中，由于NADH、ADP和Pi的代偿性变化，大脑中ATP的合成是如何维持的。11只比格犬麻醉和机械通气，并通过以20分钟的间隔逐步降低吸入O2（FIO 2）的分数诱导稳态分级缺氧。使用31 P-NMR和荧光光谱法测量生化代谢物。当矢状窦氧分压（PVO 2）降至15 Torr时，NADH升高30%，Pi升高50%，磷酸肌酸（PCr）降低20%。相反，ATP保持不变。在保持稳定体温的犬中，ADP增加了10%，但在体温随PVO 2下降而下降的犬中，ADP下降了30%。PCr/Pi与稳态缺氧时的磷酸化电位有明显的相关性。由于Michaelis-Menten方程的相互关系，对O2缺乏的补偿归因于ADP、Pi和NADH的增加。如果ADP、Pi和O2的米氏常数（Km）与体外线粒体中测定的相同，则在PVO 2为7.5 Torr时，能够维持稳态ATP的最小脑细胞溶质O2接近其Km（0.1 Torr）。在此临界O2水平下，PCr/Pi为0.9，细胞内pH为6.75，磷酸化电位为38.5 mM-1，计算的氧化磷酸化ATP形成的最大速度为正常的55%。
The relationship between biochemical and physiological responses and tissue O2 during hypoxia was investigated in vivo in the dog brain by 31P nuclear magnetic resonance (NMR) spectroscopy. Our findings demonstrate how ATP synthesis in the brain can be maintained during hypoxia because of compensatory changes in NADH, ADP, and Pi. Eleven beagle dogs were anesthetized and mechanically ventilated, and a steady-state graded hypoxia was induced by decreasing the fraction of inspired O2 (FIO2) stepwise at 20-min intervals. Biochemical metabolites were measured using 31P-NMR and fluorescence spectroscopy. When sagittal sinus O2 partial pressure (PVO2) had decreased to 15 Torr, NADH increased by 30%, Pi increased by 50%, and phosphocreatine (PCr) decreased by 20%. In contrast, ATP remained constant. There was a 10% increase in ADP in dogs that maintained a steady temperature, but ADP decreased by as much as 30% in dogs in which body temperature decreased with the falling PVO2. PCr/Pi was logarithmically related to the phosphorylation potential during steady-state hypoxia. Compensation for the O2 lack is attributed to increases in ADP, Pi, and NADH as a result of the reciprocal relationship of the Michaelis-Menten equation. If the Michaelis-Menten constants (Km) of ADP, Pi, and O2 are the same as determined in vitro in mitochondria, the minimum brain cytosolic O2 capable of maintaining a steady-state ATP is near its Km (0.1 Torr) at a PVO2 of 7.5 Torr. At this critical O2 level, PCr/Pi is 0.9, intracellular pH is 6.75, phosphorylation potential is 38.5 mM-1, and the calculated maximum velocity of ATP formation by oxidative phosphorylation is 55% of normal.