title: Increased PFK activity and GLUT4 protein content in McArdle's disease.
abstract: Inborn errors of metabolism represent an opportunity to conduct studies in order to understand compensatory adaptations to a defective metabolic pathway. We evaluated the molecular and biochemical adaptations in substrate metabolism (glycolysis, electron transport chain, tricarboxylic acid cycle, beta-oxidation) in response to myophosphorylase deficiency in skeletal muscle from 13 patients with McArdle's disease (MD) and 13 age-matched controls. MD muscle had higher phosphofructokinase protein content and activity as well as glucose transporter 4 (GLUT4) protein content and lower GLUT4 mRNA content than controls. At the protein level, skeletal muscle adaptations suggest an augmented glucose transport and glycolytic flux as a compensatory metabolic strategy to a chronic absence of muscle glycogen phosphorylase. These results support previous findings of increased glucose uptake during exercise and alleviation of symptoms with oral sucrose in patients with MD.
authors: Department of Pediatrics and Medicine, McMaster University Medical Centre, Hamilton, ON, Canada.
authors: Holly A
authors: HA
authors: Robertshaw
authors: Sandeep
authors: S
authors: Raha
authors: Jan J
authors: JJ
authors: Kaczor
authors: Mark A
authors: MA
authors: Tarnopolsky
mesh_terms: D000328:Adult; D004734:Energy Metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism*; D006012:Glycogen Storage Disease Type V / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D025221:Phosphofructokinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D025221:Phosphofructokinases; D005947:Glucose