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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenine / metabolism
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Adenosine Triphosphate / biosynthesis
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Adenylate Kinase / chemistry
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Adenylate Kinase / genetics*
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Adenylate Kinase / physiology
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Animals
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Blotting, Northern
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Catalysis
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Cloning, Molecular
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Creatine Kinase / metabolism
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Embryo, Mammalian / metabolism
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Gene Deletion*
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Glucose-6-Phosphate / metabolism
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Guanosine Diphosphate / metabolism
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Guanosine Triphosphate / metabolism
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Guanylate Kinases
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Hydrogen-Ion Concentration
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Hypoxia
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Isoenzymes / chemistry
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Isoenzymes / genetics*
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Isoenzymes / physiology
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Knockout
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Mice, Mutant Strains
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / physiology*
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Nucleoside-Phosphate Kinase / metabolism
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Phosphotransferases / metabolism
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Potassium Chloride / pharmacology
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Protein Isoforms
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Stem Cells / metabolism
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Stress, Physiological
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Time Factors
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Up-Regulation
Substances
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Isoenzymes
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Protein Isoforms
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Guanosine Diphosphate
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Glucose-6-Phosphate
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Potassium Chloride
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Guanosine Triphosphate
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Adenosine Triphosphate
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Phosphotransferases
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Creatine Kinase
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Adenylate Kinase
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adenylate kinase 1
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Nucleoside-Phosphate Kinase
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Guanylate Kinases
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Adenine