Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.,NMR in Biomedicine

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Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2020-08-16 , DOI: 10.1002/nbm.4381
Miles F Bartlett ₁ , Liam F Fitzgerald ₁ , Rajakumar Nagarajan ₂ , Jane A Kent ₁

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Several methods have been developed for using ³¹P‐MRS to calculate rates of oxidative ATP synthesis (ATP_OX) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATP_COST) remains constant or (2) Michaelis‐Menten coupling between cytosolic ADP and ATP_OX does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high‐intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATP_OX calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest‐contraction‐recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis (V_iPCr) following each trial served as the criterion measure of ATP_OX because this method makes no assumptions of constant ATP_COST or Michaelis‐Menten coupling between changes in cytosolic ADP and ATP_OX. Subsequently, we calculated ATP_OX throughout the 240 s trial using several traditional calculation methods and compared estimations of ATP_OX from each method with time‐matched measurements of V_iPCr. Method 1, which assumes that ATP_COST does not change, was able to model changes in V_iPCr over time, but showed poor accuracy for predicting V_iPCr across a wide range of ATP_OX values. In contrast, Michaelis‐Menten methods, which assume that the relationship between changes in cytosolic ADP and ATP_OX remains constant, were invalid because they could not model the decline in V_iPCr. However, adjusting these Michaelis‐Menten methods for observed changes in maximal ATP_OX capacity (i.e., V_max) permitted modeling of the decline in V_iPCr and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATP_OX can be obtained during high‐intensity contractions by adjusting Michaelis‐Menten ATP_OX calculations for changes in V_max observed from baseline to post‐fatigue.

中文翻译：

在高强度骨骼肌收缩期间计算体内氧化 ATP 合成的有效性和准确性。

已经开发了几种使用³¹ P-MRS 计算肌肉收缩期间氧化 ATP 合成速率 (ATP _OX ) 的方法，基于以下假设：(1) ATP 力量生成_成本(ATP _COST ) 保持不变或 (2) Michaelis-胞质 ADP 和 ATP _OX之间的 Menten 偶联不会改变。然而，越来越多的证据表明，在高强度疲劳方案中，这些假设中的一个或两个是无效的。因此，有必要检查传统 ATP _OX的有效性和准确性这些条件下的计算方法。为了弥补这一差距，我们在持续 24、60、120 和 240 秒的四项休息-收缩-恢复试验中测量了 9 名年轻人股外侧肌的磷酸盐浓度和 pH。每次试验后磷酸肌酸再合成的初始速度 ( V _iPCr ) 作为 ATP _OX的标准度量，因为该方法没有假设恒定的 ATP _COST或细胞溶质 ADP 和 ATP _OX变化之间的 Michaelis-Menten 耦合。随后，我们计算ATP _OX ATP的整个使用几种传统计算方法240秒试验并比较估计_OX从每个方法与V _{iPCr 的}时间匹配测量。假设 ATP _COST不变的方法 1能够模拟V _iPCr随时间的变化，但在广泛的 ATP _OX值范围内预测V _{iPCr 的}准确性较差。相比之下，Michaelis-Menten 方法假设细胞溶质 ADP 和 ATP _OX变化之间的关系保持不变，则无效，因为它们无法模拟V _iPCr的下降。然而，这些调整对于在最大ATP观察到的变化米氏方法_OX容量（即，V_最大) 允许对V _iPCr的下降进行建模并显着提高准确性。这些综合分析的结果表明，通过调整 Michaelis-Menten ATP _OX计算以适应从基线到疲劳后观察到的V _max变化，可以在高强度收缩期间获得有效、准确的 ATP _OX测量值。

更新日期：2020-10-05

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