Cell studies have implicated ADP as the key regulator of mitochondrial respiration. Yet recent in vivo NMR results have challenged that hypothesis. Myocardial experiments demonstrate the ADP concentration does not correlate with increased oxygen consumption under a variety of physiological conditions. In contrast, skeletal muscle results tend to support the role of ADP. These studies, along with many other, measure the steady state response, not the transient one. Yet, it is the transient metabolic response that will provide insight into the key regulatory steps associated with muscle contraction. We have developed an NMR strategy to follow transient metabolic changes in milliseconds. Moreover, we have developed a 1H NMR method to measure fluctuations in the intracellular oxygen with the signals of myoglobin. These to NMR advances open an opportunity to focus on the role of ADP and oxygen during a single concentration cycle. Such an investigation will illuminate our understanding of metabolic regulation in myocardial as well as skeletal muscle and will provide a novel basis for clinical treatment strategies.
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