Stimulation of myocardial coenzyme A degradation by fatty acids.
Stimulation of myocardial coenzyme A degradation by fatty acids.
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脂肪酸刺激心肌辅酶 A 降解。
DOI：
10.1152/ajpheart.1987.253.1.h41
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Neely,JR
中科院分区：
文献类型：
--
作者：
Lopaschuk,GD;Neely,JR
在已知刺激CoA合成的条件下，通过灌注45分钟，离体心脏中的辅酶A（CoA）水平从537 +/- 14增加到818 +/- 44 nmol/g干重（5）。随后，用含有葡萄糖（11 mM）和丙酮酸盐（5 mM）的缓冲液灌注这些心脏3分钟对CoA水平（789 +/- 42 nmol/g干重）没有影响。然而，灌注含有葡萄糖（11 mM）和棕榈酸（1.2 mM）的缓冲液减少CoA水平为683 +/- 34 nmol/g干重在3分钟内。这种减少CoA似乎发生在细胞溶质室与线粒体CoA含量没有变化，并与长链酰基CoA的组织含量的上升。甘油三酯中脂肪酸的掺入增加与总酰基辅酶A的升高相关，表明细胞溶质中长链酰基辅酶A水平升高。最大限度地增加酰基辅酶A水平的灌注条件也最大限度地刺激辅酶A降解。这些观察结果表明，CoA的胞质降解与该隔室中高水平的长链酰基CoA有关。在未来的研究中使用这些灌注条件将有助于确定CoA降解的途径，并确定控制CoA细胞水平的机制。
Coenzyme A (CoA) levels were increased in isolated hearts from 537 +/- 14 to 818 +/- 44 nmol/g dry wt by perfusion for 45 min under conditions known to stimulate CoA synthesis (5). Subsequently, perfusion of these hearts with buffer containing glucose (11 mM) and pyruvate (5 mM) for 3 min had no effect on CoA levels (789 +/- 42 nmol/g dry wt). However, perfusion with a buffer containing glucose (11 mM) and palmitate (1.2 mM) decreased CoA levels to 683 +/- 34 nmol/g dry wt within 3 min. This decrease in CoA appeared to occur in the cytosolic compartment with no change in mitochondrial CoA content and was associated with a rise in tissue content of long-chain acyl-CoA. An increased incorporation of fatty acids into triglycerides was associated with the rise in total acyl-CoA suggesting that long-chain acyl-CoA levels were elevated in the cytosolic compartment. Perfusion conditions which maximally increased acyl-CoA levels also maximally stimulated CoA degradation. These observations suggest that the cytosolic degradation of CoA is related to high levels of long-chain acyl-CoA in this compartment. Use of these perfusion conditions in future studies should help define the pathway of CoA degradation and determine the mechanisms which control cellular levels of CoA.