What can metabolic myopathies teach us about exercise physiology?

2006 ◽  
Vol 31 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Mark A Tarnopolsky
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Capacity ◽  
Human Skeletal Muscle ◽  
Exercise Physiology ◽  
Maximal Aerobic Capacity ◽  
Nutritional Interventions ◽  
Mcardle's Disease ◽  
Metabolic Myopathies ◽  
Myoadenylate Deaminase ◽  
Mcardle’S Disease

Exercise physiologists are interested in metabolic myopathies because they demonstrate how knocking out a component of a specific biochemical pathway can alter cellular metabolism. McArdle's disease (myophosphorylase deficiency) has often been studied in exercise physiology to demonstrate the influence of removing the major anaerobic energy supply to skeletal muscle. Studies of patients with McArdle's disease have shown the increased reliance on blood-borne fuels, the importance of glycogen to maximal aerobic capacity, and the use of nutritional strategies to bypass metabolic defects. Myoadenylate deaminase deficiency is the most common metabolic enzyme deficiency in human skeletal muscle. It is usually compensated for endogenously and does not have a major influence on high-energy power output. Nutritional interventions such as carbohydrate loading and carbohydrate supplementation during exercise are essential components of therapy for patients with fatty acid oxidation defects. Cases of mitochondrial myopathies illustrate the importance of peripheral oxygen extraction for maximal aerobic capacity and show how both exercise and nutritional interventions can partially compensate for these mutations. In summary, metabolic myopathies provide important insights into regulatory and nutritional aspects of the major biochemical pathways of intermediary metabolism in human skeletal muscle. Key words: myoadenylate deaminase deficiency, MELAS syndrome, McArdle's disease, mitochondrial disease, inborn errors of metabolism.

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity

2011 ◽  
Vol 111 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Lorenzo K. Love ◽  
Paul J. LeBlanc ◽  
J. Greig Inglis ◽  
Nicolette S. Bradley ◽  
Jon Choptiany ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Endurance Training ◽  
Aerobic Capacity ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Carbohydrate Oxidation ◽  
Pyruvate Dehydrogenase Phosphatase

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity ( r2 = 0.399, P = 0.001) and PDP1 protein expression ( r2 = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α ( r2 = 0.310, P = 0.002) and PDK2 protein ( r2 = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼18% of the variance in PDP activity ( r2 = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼38% of the variance in PDP activity ( r2 = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).

scholarly journals Progressive exercise training improves maximal aerobic capacity in individuals with well-healed burn injuries

2019 ◽  
Vol 317 (4) ◽  
pp. R563-R570 ◽  
Author(s):  
Steven A. Romero ◽  
Gilbert Moralez ◽  
Manall F. Jaffery ◽  
Mu Huang ◽  
Matthew N. Cramer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Surface Area ◽  
Body Surface Area ◽  
Aerobic Capacity ◽  
Body Surface ◽  
Burn Injuries ◽  
Maximal Aerobic Capacity ◽  
Area Burned ◽  
Progressive Exercise

Long-term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-mo community-based exercise training program will increase maximal aerobic capacity (V̇o2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and postexercise training in noninjured control subjects ( n = 11) and in individuals with well-healed burn injuries ( n = 13, moderate body surface area burned; n = 20, high body surface area burned). Exercise training increased V̇o2max in all groups (control: 15 ± 5%; moderate body surface area: 11 ± 3%; high body surface area: 11 ± 2%; P < 0.05), though the magnitude of this improvement did not differ between groups ( P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase ( P < 0.05) and cytochrome c oxidase ( P < 0.05), an effect that did not differ between groups ( P = 0.2). These data suggest that 6 mo of progressive exercise training improves V̇o2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

McArdle's disease with myoadenylate deaminase deficiency: Observations in a combined enzyme deficiency

Neurology ◽  
1987 ◽  
Vol 37 (6) ◽  
pp. 1039-1039 ◽  
Author(s):  
S. L. Heller ◽  
K. K. Kaiser ◽  
G. J. Planer ◽  
J. M. Hagberg ◽  
M. H. Brooke
Keyword(s):  
Enzyme Deficiency ◽  
Myoadenylate Deaminase Deficiency ◽  
Mcardle's Disease ◽  
Myoadenylate Deaminase ◽  
Mcardle’S Disease

The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue

1986 ◽  
Vol 61 (2) ◽  
pp. 391-401 ◽  
Author(s):  
S. F. Lewis ◽  
R. G. Haller
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fatigue ◽  
Muscle Afferents ◽  
Common Denominator ◽  
Circulatory Response ◽  
Mcardle's Disease ◽  
O2 Transport ◽  
Mcardle’S Disease ◽  
Muscle Phosphorylase ◽  
Response To Exercise

Muscle phosphorylase deficiency (McArdle's disease) has conventionally been considered a disorder of glycogenolysis, and the associated impairment in oxidative metabolism has been largely overlooked. Muscle glycogen normally is the primary oxidative fuel at exercise work loads requiring more than 75–80% of maximal O2 uptake (VO2max). Evidence is presented to support the hypothesis that a limited flux through the Embden-Myerhof pathway in McArdle's disease reduces the capacity to generate NADH required to support a normal VO2max. The extent of the oxidative defect is substrate dependent; i.e., it can be partially corrected by increasing the availability of alternative oxidative substrates (e.g., glucose, free fatty acids) to working muscle. Experiments employing modification of substrate availability closely link the hyperkinetic circulatory response to exercise (i.e., an abnormally large increase in O2 transport to skeletal muscle) and the premature muscle fatigue and cramping of McArdle patients with their oxidative impairment and suggest that a metabolic common denominator in these abnormal responses may be a pronounced decline in the muscle phosphorylation potential ([ATP]/[ADP][Pi]). The hyperkinetic circulation likely is mediated by the local effects on metabolically sensitive skeletal muscle afferents and vascular smooth muscle of K+, Pi, or adenosine or a combination of these substances released excessively from working skeletal muscle. The premature muscle fatigue and cramping of McArdle patients does not appear to be due to depletion of ATP but is associated with an increased accumulation of Pi and probably ADP in skeletal muscle. Accumulations of Pi and ADP are known to inhibit the myofibrillar, Ca2+, and Na+-K+-ATPase reactions.

Breakdown of adenine nucleotide pool in fatiguing skeletal muscle in McArdle's disease: A noninvasive31P-MRS and EMG study

2003 ◽  
Vol 27 (6) ◽  
pp. 728-736 ◽  
Author(s):  
Jochen Zange ◽  
Torsten Grehl ◽  
Catherine Disselhorst-Klug ◽  
Günter Rau ◽  
Klaus Müller ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adenine Nucleotide ◽  
Mcardle's Disease ◽  
Mcardle’S Disease ◽  
Adenine Nucleotide Pool

scholarly journals Aerobic capacity and telomere length in human skeletal muscle and leukocytes across the lifespan

Aging ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 359-369 ◽  
Author(s):  
Danielle Hiam ◽  
Cassandra Smith ◽  
Sarah Voisin ◽  
Josh Denham ◽  
Xu Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Telomere Length ◽  
Aerobic Capacity ◽  
Human Skeletal Muscle

Ischaemic exercise test in myoadenylate deaminase deficiency and McArdle's disease: measurement of plasma adenosine, inosine and hypoxanthine

1986 ◽  
Vol 70 (4) ◽  
pp. 399-401 ◽  
Author(s):  
S. P. T. Sinkeler ◽  
E. M. G. Joosten ◽  
R. A. Wevers ◽  
R. A. Binkhorst ◽  
F. T. Oerlemans ◽  
...  
Keyword(s):  
Exercise Test ◽  
Diagnostic Value ◽  
Myoadenylate Deaminase Deficiency ◽  
Control Subjects ◽  
Mcardle's Disease ◽  
Before And After ◽  
Myoadenylate Deaminase ◽  
Mcardle’S Disease ◽  
Forearm Exercise ◽  
Plasma Adenosine

1. Plasma adenosine, inosine and hypoxanthine concentrations were assayed in seven control subjects, five myoadenylate deaminase deficient (MADD) patients and six McArdle patients before and after ischaemic forearm exercise. 2. The plasma adenosine increase was very low in all test groups and there were no significant differences. 3. The MADD patients showed a significantly lower increase of plasma inosine and hypoxanthine after exercise as compared with the controls. 4. In the McArdle patients the increase in plasma inosine and hypoxanthine after exercise did not differ significantly from the values measured in the controls. 5. The ischaemic exercise test with measurement of plasma inosine and hypoxanthine might be of diagnostic value in MADD, but not in McArdle's disease.

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