In Vivo Skeletal Muscle Oxidative and Glycolytic ATP Synthesis in Young and Older Adults

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S521
Author(s):  
Ian R. Lanza ◽  
Douglas E. Befroy ◽  
Danielle M. Wigmore ◽  
Jane A. Kent-Braun
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Atp Synthesis ◽  
Glycolytic Atp

scholarly journals Increased Glycolytic ATP Synthesis Is Associated with Tafenoquine Resistance inLeishmania major

2011 ◽  
Vol 55 (3) ◽  
pp. 1045-1052 ◽  
Author(s):  
José Ignacio Manzano ◽  
Luis Carvalho ◽  
José M. Pérez-Victoria ◽  
Santiago Castanys ◽  
Francisco Gamarro
Keyword(s):  
Leishmania Major ◽  
Alternative Therapy ◽  
Atp Synthesis ◽  
Drug Efflux ◽  
Wild Type ◽  
Mechanisms Of Resistance ◽  
Glycolytic Atp ◽  
Drug Free

ABSTRACTTafenoquine (TFQ), an 8-aminoquinoline used to treat and preventPlasmodiuminfections, could represent an alternative therapy for leishmaniasis. Indeed, TFQ has shown significant leishmanicidal activity bothin vitroandin vivo, where it targetsLeishmaniamitochondria and activates a final apoptosis-like process. In order not to jeopardize the life span of this potential antileishmania drug, it is important to determine the likelihood thatLeishmaniawill develop resistance to TFQ and the mechanisms of resistance induced. To address this issue, a TFQ-resistantLeishmania majorpromastigote line (R4) was selected. This resistance, which is unstable in a drug-free medium (revertant line), was maintained in intramacrophage amastigote forms, and R4 promastigotes were found to be cross-resistant to other 8-aminoquinolines. A decreased TFQ uptake, which is probably associated with an alkalinization of the intracellular pH rather than drug efflux, was observed for both the R4 and revertant lines. TFQ induces a decrease in ATP synthesis in allLeishmanialines, although total ATP levels were maintained at higher values in R4 parasites. In contrast, ATP synthesis by glycolysis was significantly increased in R4 parasites, whereas mitochondrial ATP synthesis was similar to that in wild-type parasites. We therefore conclude that increased glycolytic ATP synthesis is the main mechanism underlying TFQ resistance inLeishmania.

scholarly journals Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action

1997 ◽  
Vol 83 (3) ◽  
pp. 867-874 ◽  
Author(s):  
T. W. Ryschon ◽  
M. D. Fowler ◽  
R. E. Wysong ◽  
A.-R. Anthony ◽  
R. S. Balaban
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Production Rate ◽  
Human Skeletal Muscle ◽  
Atp Synthesis ◽  
High Energy ◽  
High Energy Phosphates ◽  
Muscle Action ◽  
Atp Production

Ryschon, T. W., Fowler, R. E. Wysong, A.-R. Anthony, and R. S. Balaban. Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action. J. Appl. Physiol. 83(3): 867–874, 1997.—The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 ± 1.3% in concentric and 34.7 ± 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action.

scholarly journals A Fish-Derived Protein Hydrolysate Induces Postprandial Aminoacidaemia and Skeletal Muscle Anabolism in an In Vitro Cell Model Using Ex Vivo Human Serum

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 647
Author(s):  
Matthew J. Lees ◽  
David Nolan ◽  
Miryam Amigo-Benavent ◽  
Conor J. Raleigh ◽  
Neda Khatib ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Human Serum ◽  
Body Mass ◽  
Ex Vivo ◽  
Protein Hydrolysate ◽  
C2c12 Myotubes ◽  
The Impact

Fish-derived proteins, particularly fish protein hydrolysates (FPH), offer potential as high-quality sources of dietary protein, whilst enhancing economic and environmental sustainability. This study investigated the impact of a blue whiting-derived protein hydrolysate (BWPH) on aminoacidaemia in vivo and skeletal muscle anabolism in vitro compared with whey protein isolate (WPI) and an isonitrogenous, non-essential amino acid (NEAA) control (0.33 g·kg−1·body mass−1) in an ex vivo, in vitro experimental design. Blood was obtained from seven healthy older adults (two males, five females; age: 72 ± 5 years, body mass index: 24.9 ± 1.6 kg·m2) in three separate trials in a randomised, counterbalanced, double-blind design. C2C12 myotubes were treated with ex vivo human serum-conditioned media (20%) for 4 h. Anabolic signalling (phosphorylation of mTOR, p70S6K, and 4E-BP1) and puromycin incorporation were determined by immunoblotting. Although BWPH and WPI both induced postprandial essential aminoacidaemia in older adults above the NEAA control, peak and area under the curve (AUC) leucine and essential amino acids were more pronounced following WPI ingestion. Insulin was elevated above baseline in WPI and BWPH only, a finding reinforced by higher peak and AUC values compared with NEAA. Muscle protein synthesis, as measured by puromycin incorporation, was greater after incubation with WPI-fed serum compared with fasted serum (P = 0.042), and delta change was greater in WPI (P = 0.028) and BWPH (P = 0.030) compared with NEAA. Myotube hypertrophy was greater in WPI and BWPH compared with NEAA (both P = 0.045), but was similar between bioactive conditions (P = 0.853). Taken together, these preliminary findings demonstrate the anabolic potential of BWPH in vivo and ex vivo, thus providing justification for larger studies in older adults using gold-standard measures of acute and chronic MPS in vivo.

scholarly journals Magnitude and control of mitochondrial sensitivity to ADP

2009 ◽  
Vol 297 (3) ◽  
pp. E774-E784 ◽  
Author(s):  
Jeroen A. L. Jeneson ◽  
Joep P. J. Schmitz ◽  
Nicole M. A. van den Broek ◽  
Natal A. W. van Riel ◽  
Peter A. J. Hilbers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
In Silico ◽  
Adenine Nucleotide ◽  
Atp Synthesis ◽  
Model Parameters ◽  
Kinetic Properties ◽  
Mitochondrial Enzymes ◽  
Concentration Changes ◽  
Multiparametric Sensitivity Analysis

The transduction function for ADP stimulation of mitochondrial ATP synthesis in skeletal muscle was reconstructed in vivo and in silico to investigate the magnitude and origin of mitochondrial sensitivity to cytoplasmic ADP concentration changes. Dynamic in vivo measurements of human leg muscle phosphocreatine (PCr) content during metabolic recovery from contractions were performed by 31P-NMR spectroscopy. The cytoplasmic ADP concentration ([ADP]) and rate of oxidative ATP synthesis (Jp) at each time point were calculated from creatine kinase equilibrium and the derivative of a monoexponential fit to the PCr recovery data, respectively. Reconstructed [ADP]-Jp relations for individual muscles containing more than 100 data points were kinetically characterized by nonlinear curve fitting yielding an apparent kinetic order and ADP affinity of 1.9 ± 0.2 and 0.022 ± 0.003 mM, respectively (means ± SD; n = 6). Next, in silico [ADP]-Jp relations for skeletal muscle were generated using a computational model of muscle oxidative ATP metabolism whereby model parameters corresponding to mitochondrial enzymes were randomly changed by 50–150% to determine control of mitochondrial ADP sensitivity. The multiparametric sensitivity analysis showed that mitochondrial ADP ultrasensitivity is an emergent property of the integrated mitochondrial enzyme network controlled primarily by kinetic properties of the adenine nucleotide translocator.

Selective PPARδ agonist treatment increases skeletal muscle lipid metabolism without altering mitochondrial energy coupling: an in vivo magnetic resonance spectroscopy study

2007 ◽  
Vol 293 (5) ◽  
pp. E1256-E1264 ◽  
Author(s):  
Beat M. Jucker ◽  
Dewen Yang ◽  
Warren M. Casey ◽  
Alan R. Olzinski ◽  
Carolyn Williams ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Uncoupling Protein ◽  
Coupling Efficiency ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
Resonance Spectroscopy ◽  
High Dose ◽  
Muscle Lipid

Peroxisome proliferator-activated receptor-δ (PPARδ) activation results in upregulation of genes associated with skeletal muscle fatty acid oxidation and mitochondrial uncoupling. However, direct, noninvasive assessment of lipid metabolism and mitochondrial energy coupling in skeletal muscle following PPARδ stimulation has not been examined. Therefore, in this study we examined the response of a selective PPARδ agonist (GW610742X at 5 or 100 mg·kg−1·day−1 for 8 days) on skeletal-muscle lipid metabolism and mitochondrial coupling efficiency in rats by using in vivo magnetic resonance spectroscopy (MRS). There was a decrease in the intramyocellular lipid-to-total creatine ratio as assessed by in vivo 1H-MRS in soleus and tibialis anterior muscles by day 7 (reduced by 49 and 46%, respectively; P < 0.01) at the high dose. Following the 1H-MRS experiment ( day 8), [1-13C]glucose was administered to conscious rats to assess metabolism in the soleus muscle. The relative fat-vs.-carbohydrate oxidation rate increased in a dose-dependent manner (increased by 52 and 93% in the 5 and 100 mg·kg−1·day−1 groups, respectively; P < 0.05). In separate experiments where mitochondrial coupling was assessed in vivo ( day 7), 31P-MRS was used to measure hindlimb ATP synthesis and 13C-MRS was used to measure the hindlimb tricarboxylic acid cycle flux (Vtca). There was no alteration, at either dose, in mitochondrial coupling efficiency measured as the ratio of unidirectional ATP synthesis flux to Vtca. Soleus muscle GLUT4 expression was decreased by twofold, whereas pyruvate dehydrogenase kinase 4, carnitine palmitoyl transferase 1a, and uncoupling protein 2 and 3 expression was increased by two- to threefold at the high dose ( P < 0.05). In summary, these are the first noninvasive measurements illustrating a selective PPARδ-mediated decrease in muscle lipid content that was consistent with a shift in metabolic substrate utilization from carbohydrate to lipid. However, the mitochondrial-energy coupling efficiency was not altered in the presence of increased uncoupling protein expression.

Validity and accuracy of calculating oxidative ATP synthesis in vivo during high‐intensity skeletal muscle contractions

2020 ◽  
Vol 33 (11) ◽  
Author(s):  
Miles F. Bartlett ◽  
Liam F. Fitzgerald ◽  
Rajakumar Nagarajan ◽  
Jane A. Kent
Keyword(s):  
Skeletal Muscle ◽  
High Intensity ◽  
Atp Synthesis ◽  
Muscle Contractions

scholarly journals Skeletal Muscle Mitochondrial Adaptations to Maximal Strength Training in Older Adults

2020 ◽  
Vol 75 (12) ◽  
pp. 2269-2277
Author(s):  
Ole Kristian Berg ◽  
Oh Sung Kwon ◽  
Thomas J Hureau ◽  
Heather L Clifton ◽  
Taylor S Thurston ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Strength Training ◽  
Complex I ◽  
Production Efficiency ◽  
Citrate Synthase ◽  
Resonance Spectroscopy ◽  
Maximal Strength ◽  
Mitochondrial Adaptations

Abstract Maximal strength training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria are still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo 31P magnetic resonance spectroscopy (31P-MRS), and gas exchange. As anticipated, MST resulted in an increased isometric knee-extensor force from 133 ± 36 to 147 ± 49 Nm (p &lt; .05) and quadriceps muscle volume from 1,410 ± 103 to 1,555 ± 455 cm3 (p &lt; .05). Mitochondrial complex (I–V) protein abundance and citrate synthase activity were not significantly altered by MST. Assessed ex vivo, maximal ADP-stimulated respiration (state 3CI+CII, PRE: 23 ± 6 and POST: 14 ± 5 ρM·mg−1·s−1, p &lt; .05), was decreased by MST, predominantly, as a result of a decline in complex I-linked respiration (p &lt; .05). Additionally, state 3 free-fatty acid linked respiration was decreased following MST (PRE: 19 ± 5 and POST: 14 ± 3 ρM·mg−1·s−1, p &lt; .05). Assessed in vivo, MST slowed the PCr recovery time constant (PRE: 49 ± 13 and POST: 57 ± 16 seconds, p &lt; .05) and lowered, by ~20% (p = .055), the quadriceps peak rate of oxidative ATP synthesis, but did not significantly alter the oxidation of lipid. Although these, likely qualitative, mitochondrial adaptations are potentially negative in terms of skeletal muscle energetic capacity, they need to be considered in light of the many improvements in muscle function that MST affords older adults.

scholarly journals Regulation of metabolism: the rest-to-work transition in skeletal muscle

2015 ◽  
Vol 309 (9) ◽  
pp. E793-E801 ◽  
Author(s):  
David F. Wilson
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Atp Synthesis ◽  
Creatine Phosphate ◽  
Valuable Insight ◽  
Metabolic Homeostasis ◽  
Lag Period ◽  
Metabolic Behavior

Mitochondrial oxidative phosphorylation is programmed to set and maintain metabolic homeostasis, and understanding that program is essential for an integrated view of cellular and tissue metabolism. The behavior predicted by a mechanism-based model for oxidative phosphorylation is compared with that experimentally measured for skeletal muscle when work is initiated. For the model, initiation of work is simulated by imposing a rate of ATP utilization of either 0.6 (equivalent of 13.4 ml O2·100 g tissue−1·min−1 or 6 μmol O2·g tissue−1·min−1) or 0.3 mM ATP/s. Creatine phosphate ([CrP]) decrease, both experimentally measured and predicted by the model, can be fit to a single exponential. Increase in ATP synthesis begins immediately but can show a “lag period,” during which the rate accelerates. The length of the lag period is similar for both experiment and model; in the model, the lag depends on intramitochondrial [NAD+]/[NADH], mitochondrial content, and size of the creatine pool ([CrP] + [Cr]) as well as the resting [CrP]/[Cr]. For in vivo conditions, increase in oxygen consumption may be linearly correlated with a decrease in [CrP] and an increase in inorganic phosphate ([Pi]) and [Cr]. The decrease in [CrP], resting and working steady state [CrP], and the increase in oxygen consumption are dependent on the Po2 in the inspired gas (experimental) or tissue Po2 (model). The metabolic behavior predicted by the model is consistent with available experimental measurements in muscle upon initiation of work, with the model providing valuable insight into how metabolic homeostasis is set and maintained.

Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis

1995 ◽  
Vol 78 (6) ◽  
pp. 2131-2139 ◽  
Author(s):  
C. H. Thompson ◽  
G. J. Kemp ◽  
A. L. Sanderson ◽  
G. K. Radda
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Maximum Rate ◽  
Atp Synthesis ◽  
Resonance Spectroscopy ◽  
Mitochondrial Regulation ◽  
Cardiac Infarction ◽  
Theoretical Approaches

To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study phosphocreatine (PCr) recovery in rat leg muscle after sciatic nerve stimulation at 1-4 Hz. We studied normal animals and animals with defective skeletal muscle mitochondrial function after experimental cardiac infarction. To analyze these data, we used three current theoretical approaches to the control of mitochondrial ATP synthesis, based on its hyperbolic relationship to cytosolic ADP concentration and on its linear relationships to PCr concentration and the free energy of ATP hydrolysis. The mitochondrial ADP concentration for one-half maximum rate of ATP synthesis appeared at least twice as high as the 30 microM expected from in vitro studies. According to all three approaches, the apparent maximum rate of ATP synthesis was independent of stimulation frequency and end-exercise pH and PCr and ADP concentrations and was reduced by approximately 50% after experimental cardiac infarction. Analysis of PCr recovery kinetics is a robust and practical way to study mitochondrial regulation and to quantify effective mitochondrial defects in vivo.

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