guanosine-diphosphate and Hypoxia

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.

Topics: Adenine; Adenosine Triphosphate; Adenylate Kinase; Animals; Blotting, Northern; Catalysis; Cloning, Molecular; Creatine Kinase; Embryo, Mammalian; Gene Deletion; Glucose-6-Phosphate; Guanosine Diphosphate; Guanosine Triphosphate; Guanylate Kinases; Hydrogen-Ion Concentration; Hypoxia; Isoenzymes; Magnetic Resonance Spectroscopy; Mice; Mice, Knockout; Mice, Mutant Strains; Muscle, Skeletal; Nucleoside-Phosphate Kinase; Phosphotransferases; Potassium Chloride; Protein Isoforms; Stem Cells; Stress, Physiological; Time Factors; Up-Regulation