DIABETES AND CONTROL OF PYRUVATE-DEHYDROGENASE IN RAT-HEART MITOCHONDRIA BY CONCENTRATION RATIOS OF ADENOSINE TRIPHOSPHATE-ADENOSINE DIPHOSPHATE, OF REDUCED-OXIDIZED NICOTINAMIDE-ADENINE DINUCLEOTIDE AND OF ACETYL-COENZYME-A-COENZYME-A
DIABETES AND CONTROL OF PYRUVATE-DEHYDROGENASE IN RAT-HEART MITOCHONDRIA BY CONCENTRATION RATIOS OF ADENOSINE TRIPHOSPHATE-ADENOSINE DIPHOSPHATE, OF REDUCED-OXIDIZED NICOTINAMIDE-ADENINE DINUCLEOTIDE AND OF ACETYL-COENZYME-A-COENZYME-A
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DOI：
10.1042/bj1640509
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发表时间：
1977-01-01
影响因子：
4.1
通讯作者：
RANDLE, PJ
中科院分区：
文献类型：
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作者：
KERBEY, AL;RADCLIFFE, PM;RANDLE, PJ
大鼠心脏线粒体中活性（去磷酸化）丙酮酸脱氢酶[EC 1.2.4.1]的比例与ATP/ADP、NADH/NAD+和乙酰CoA/CoA的总浓度比相关。这些代谢产物用ATP依赖性和NADH依赖性的双磷酸酶测定。在[ATP]/[ADP]和[乙酰辅酶A]/[CoA]恒定时，NADH/NAD+浓度比的增加与丙酮酸脱氢酶磷酸化和失活的增加有关。这是基于与0.4 mM-或1 mM-琥珀酸盐孵育的线粒体和与0.4 mM-琥珀酸盐孵育的线粒体之间的比较。鱼藤酮在恒定的[ATP]/[ADP]和[NADH]/[NAD+]下，乙酰辅酶A/辅酶A浓度比的增加与丙酮酸脱氢酶磷酸化和失活的增加有关。这是基于在50 μ M-棕榈酰-L-肉毒碱和250 μ M-2-酮戊二酸+50 μ M-L-苹果酸中孵育之间的比较。这些发现与高[NADH]/[NAD+]和[乙酰辅酶A]/[CoA]比率激活丙酮酸脱氢酶激酶反应一致。比较糖尿病和非糖尿病大鼠心肌线粒体，发现在四氧嘧啶糖尿病中，除了ATP/ADP、NADH/ NAD+或乙酰辅酶A/辅酶A浓度比以外，还有其他因素可增强丙酮酸脱氢酶的磷酸化和失活。
The proportion of active (dephosphorylated) pyruvate dehydrogenase [EC 1.2.4.1] in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4 mM- or 1mM-succinate and mitochondria incubated with 0.4 mM-succinate .+-. rotenone. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH]/[NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 .mu.M-palmitoyl-L-carnitine and in 250 .mu.M-2-oxoglutarate + 50 .mu.M-L-malate. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyrvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/ NAD+ or acetyl-CoA/CoA.