| 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 | Holly A Robertshaw, Sandeep Raha, Jan J Kaczor, Mark A Tarnopolsky
(Affiliation: Department of Pediatrics and Medicine, McMaster University Medical Centre, Hamilton, ON, Canada.)
|
| Journal | Muscle & nerve
(Muscle Nerve)
Vol. 37
Issue 4
Pg. 431-7
(Apr 2008)
ISSN: 0148-639X United States |
| PMID | 18067156
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Glucose Transporter Type 4
- RNA, Messenger
- SLC2A4 protein, human
- Glucose
- Phosphofructokinases
|
| Topics |
- Adult
- Energy Metabolism
(physiology)
- Enzyme Activation
(physiology)
- Female
- Glucose
(metabolism)
- Glucose Transporter Type 4
(genetics, metabolism)
- Glycogen Storage Disease Type V
(metabolism, physiopathology)
- Humans
- Male
- Middle Aged
- Muscle, Skeletal
(enzymology)
- Phosphofructokinases
(genetics, metabolism)
- RNA, Messenger
(metabolism)
|
