title: Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement.
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.
authors: 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.
authors: E
authors: E
authors: Janssen
authors: P P
authors: PP
authors: Dzeja
authors: F
authors: F
authors: Oerlemans
authors: A W
authors: AW
authors: Simonetti
authors: A
authors: A
authors: Heerschap
authors: A
authors: A
authors: de Haan
authors: P S
authors: PS
authors: Rush
authors: R R
authors: RR
authors: Terjung
authors: B
authors: B
authors: Wieringa
authors: A
authors: A
authors: Terzic
mesh_terms: D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000263:Adenylate Kinase / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D002384:Catalysis; D003001:Cloning, Molecular; D003402:Creatine Kinase / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D017353:Gene Deletion; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D051528:Guanylate Kinases; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms; D013234:Stem Cells / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D020033:Protein Isoforms; D006153:Guanosine Diphosphate; D019298:Glucose-6-Phosphate; D011189:Potassium Chloride; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D003402:Creatine Kinase; D000263:Adenylate Kinase; C110939:adenylate kinase 1; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D000225:Adenine