Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement |
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| Authors: | Janssen E Dzeja P P Oerlemans F Simonetti A W Heerschap A de Haan A Rush P S Terjung R R Wieringa B Terzic A |
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| Affiliation: | Departments of Cell Biology and Diagnostic Radiology, University Medical Center, University of Nijmegen, Institute for Fundamental and Clinical Human Movement Sciences, Vrije University Amsterdam, The Netherlands. |
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| Abstract: | Efficient cellular energy homeostasis is a critical determinant of muscle performance, providing evolutionary advantages responsible for species survival. Phosphotransfer reactions, which couple ATP production and utilization, are thought to play a central role in this process. Here, we provide evidence that genetic disruption of AK1-catalyzed ss-phosphoryl transfer in mice decreases the potential of myofibers to sustain nucleotide ratios despite up-regulation of high-energy phosphoryl flux through glycolytic, guanylate and creatine kinase phosphotransfer pathways. A maintained contractile performance of AK1-deficient muscles was associated with higher ATP turnover rate and larger amounts of ATP consumed per contraction. Metabolic stress further aggravated the energetic cost in AK1(-/-) muscles. Thus, AK1-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy, enabling skeletal muscle to perform at the lowest metabolic cost. |
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| Keywords: | adenylate kinase creatine kinase energy homeostasis knockout mice phosphoryl transfer |
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