scholarly journals Complex I is bypassed during high intensity exercise

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Avlant Nilsson ◽  
Elias Björnson ◽  
Mikael Flockhart ◽  
Filip J. Larsen ◽  
Jens Nielsen
Keyword(s):  
High Intensity ◽  
Complex I ◽  
Atp Synthesis ◽  
Metabolic Model ◽  
High Intensity Exercise ◽  
Whole Body ◽  
Synthesis Rate ◽  
Proteomics Data ◽  
Exercise Tests

Abstract Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.

Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise

2007 ◽  
Vol 293 (1) ◽  
pp. R392-R401 ◽  
Author(s):  
Andrew M. Jones ◽  
Daryl P. Wilkerson ◽  
Nicolas J. Berger ◽  
Jonathan Fulford
Keyword(s):  
Endurance Training ◽  
High Intensity ◽  
Slow Component ◽  
Knee Extension ◽  
High Intensity Exercise ◽  
Whole Body ◽  
Time To Exhaustion ◽  
Exercise Tests ◽  
Before And After ◽  
Knee Extension Exercise

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 ± 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 ± 2.3 min vs. postintervention group (POST): 19.4 ± 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 ± 1.6 min vs. POST: 22.0 ± 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 ± 13 s vs. POST: 43 ± 10 s) or the trained leg (PRE: 38 ± 8 s vs. POST: 40 ± 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 ± 7 vs. POST: 7 ± 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 ± 8 vs. POST: 12 ± 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.

scholarly journals Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

2008 ◽  
Vol 54 (2) ◽  
pp. 292-300 ◽  
Author(s):  
Renke Maas ◽  
Edzard Schwedhelm ◽  
Lydia Kahl ◽  
Huige Li ◽  
Ralf Benndorf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Urinary Excretion ◽  
Indirect Evidence ◽  
No Oxidation ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Synthesis Rate ◽  
No Production

Abstract Background: Endothelial function is impaired in hypercholesterolemia and atherosclerosis. Based on mostly indirect evidence, this impairment is attributed to reduced synthesis or impaired biological activity of endothelium-derived nitric oxide (NO). It was the aim of this study to directly estimate and compare whole-body NO production in normo- and hypercholesterolemia by applying a nonradioactive stable isotope dilution technique in vivo. Methods: We enrolled 12 normocholesterolemic and 24 hypercholesterolemic volunteers who were all clinically healthy. To assess whole-body NO synthesis, we intravenously administered l-[guanidino-(15N2)]-arginine and determined the urinary excretion of 15N-labeled nitrate, the specific end product of NO oxidation in humans, by use of gas chromatography-mass spectrometry. In addition, we measured flow-mediated vasodilation (FMD) of the brachial artery, expression of endothelial NOS (eNOS) in platelets, plasma concentration of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), and urinary excretion of 8-isoprostaglandin F2α (8-iso-PGF2α). Results: After infusion of l-[guanidino-(15N2)]-arginine, cumulative excretion of 15N-labeled-nitrate during 48 h was 40% [95% CI 15%–66%] lower in hypercholesterolemic than normocholesterolemic volunteers [mean 9.2 (SE 0.8) μmol vs 15.4 (2.3) μmol/l, P = 0.003]. FMD was on average 36% [4%–67%] lower in hypercholesterolemic than normocholesterolemic volunteers [6.3 (4.0)% vs 9.4 (4.6)%, P = 0.027]. Normalized expression of NOS protein in platelets was also significantly lower in hypercholesterolemic volunteers, whereas there were no significant differences in plasma ADMA concentration or urinary excretion of 8-iso-PGF2α between the 2 groups. Conclusions: This study provides direct evidence for a decreased whole body NO synthesis rate in healthy people with hypercholesterolemia.

scholarly journals Aerobic Growth of Escherichia coli Is Reduced, and ATP Synthesis Is Selectively Inhibited when Five C-terminal Residues Are Deleted from the ϵ Subunit of ATP Synthase

2015 ◽  
Vol 290 (34) ◽  
pp. 21032-21041 ◽  
Author(s):  
Naman B. Shah ◽  
Thomas M. Duncan
Keyword(s):  
Escherichia Coli ◽  
Atp Synthase ◽  
Atp Hydrolysis ◽  
Atp Synthesis ◽  
Intrinsic Rate ◽  
Synthesis Rate ◽  
Final Segment ◽  
Rotary Catalysis

F-type ATP synthases are rotary nanomotor enzymes involved in cellular energy metabolism in eukaryotes and eubacteria. The ATP synthase from Gram-positive and -negative model bacteria can be autoinhibited by the C-terminal domain of its ϵ subunit (ϵCTD), but the importance of ϵ inhibition in vivo is unclear. Functional rotation is thought to be blocked by insertion of the latter half of the ϵCTD into the central cavity of the catalytic complex (F1). In the inhibited state of the Escherichia coli enzyme, the final segment of ϵCTD is deeply buried but has few specific interactions with other subunits. This region of the ϵCTD is variable or absent in other bacteria that exhibit strong ϵ-inhibition in vitro. Here, genetically deleting the last five residues of the ϵCTD (ϵΔ5) caused a greater defect in respiratory growth than did the complete absence of the ϵCTD. Isolated membranes with ϵΔ5 generated proton-motive force by respiration as effectively as with wild-type ϵ but showed a nearly 3-fold decrease in ATP synthesis rate. In contrast, the ϵΔ5 truncation did not change the intrinsic rate of ATP hydrolysis with membranes. Further, the ϵΔ5 subunit retained high affinity for isolated F1 but reduced the maximal inhibition of F1-ATPase by ϵ from >90% to ∼20%. The results suggest that the ϵCTD has distinct regulatory interactions with F1 when rotary catalysis operates in opposite directions for the hydrolysis or synthesis of ATP.

Effects of high-amount–high-intensity exercise on in vivo platelet activation: Modulation by lipid peroxidation and AGE/RAGE axis

2013 ◽  
Vol 110 (12) ◽  
pp. 1232-1240 ◽  
Author(s):  
Francesca Santilli ◽  
Natale Vazzana ◽  
Pierpaolo Iodice ◽  
Stefano Lattanzio ◽  
Rossella Liani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Exercise Training ◽  
Platelet Activation ◽  
High Intensity ◽  
Plasma Levels ◽  
High Intensity Exercise ◽  
Similar Amount ◽  
Activation Markers

SummaryPhysical activity is associated with cardiovascular risk reduction, but the effects of exercise on platelet activation remain controversial. We investigated the effects of regular high-amount, high intensity aerobic exercise on in vivo thromboxane (TX)-dependent platelet activation and plasma levels of platelet-derived proteins, CD40L and P-selectin, and whether platelet variables changes may be related to changes in high-density lipoprotein (HDL) and in the extent of oxidative stress and oxidative stress-related inflammation, as reflected by urinary isoprostane excretion and endogenous soluble receptor for advanced glycation end-products (esRAGE), respectively. Urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α and plasma levels of P-selectin, CD40L and esRAGE were measured before and after a eight-week standardised aerobic high-amount–high-intensity training program in 22 sedentary subjects with low-to-intermediate risk. Exercise training had a clear beneficial effect on HDL cholesterol (+10%, p=0.027) and triglyceride (-27%, p=0.008) concentration. In addition, a significant (p<0.0001) decrease in urinary 11-dehydro-TXB2 (26%), 8-iso-PGF2α (21 %), plasma P-selectin (27%), CD40L (35%) and a 61% increase in esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso-PGF2α [beta=0.33, SEM=0.116, p=0.027] and esRAGE (beta=-0.30, SEM=31.3, p=0.046) were the only significant predictors of urinary 11-dehydro-TXB2 excretion rate over the training period. In conclusion, regular high-amount–high-intensity exercise training has broad beneficial effects on platelet activation markers, paralleled and possibly associated with changes in the lipoprotein profile and in markers of lipid peroxidation and AGE/RAGE axis. Our findings may help explaining why a similar amount of exercise exerts significant benefits in preventing cardiovascular events.

scholarly journals Nuclear Expression of a Mitochondrial DNA Gene: Mitochondrial Targeting of Allotopically Expressed Mutant ATP6 in Transgenic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
David A. Dunn ◽  
Carl A. Pinkert
Keyword(s):  
Mitochondrial Dna ◽  
Atp Synthesis ◽  
Serum Lactate ◽  
Superior Performance ◽  
Synthesis Rate ◽  
Mitochondrial Targeting ◽  
Biochemical Tests ◽  
Balance Beam ◽  
Protein Levels

Nuclear encoding of mitochondrial DNA transgenes followed by mitochondrial targeting of the expressed proteins (allotopic expression; AE) represents a potentially powerful strategy for creating animal models of mtDNA disease. Mice were created that allotopically express either a mutant (A6M) or wildtype (A6W)mt-Atp6transgene. Compared to non-transgenic controls, A6M mice displayed neuromuscular and motor deficiencies (wire hang, pole, and balance beam analyses;P<0.05), no locomotor differences (gait analysis;P<0.05) and enhanced endurance in Rota-Rod evaluations (P<0.05). A6W mice exhibited inferior muscle strength (wire hang test;P<0.05), no difference in balance beam footsteps, accelerating Rota-Rod, pole test and gait analyses; (P<0.05) and superior performance in balance beam time-to-cross and constant velocity Rota-Rod analyses (P<0.05) in comparison to non-transgenic control mice. Mice of both transgenic lines did not differ from non-transgenic controls in a number of bioenergetic and biochemical tests including measurements of serum lactate and mitochondrial MnSOD protein levels, ATP synthesis rate, and oxygen consumption (P>0.05). This study illustrates a mouse model capable of circumventingin vivomitochondrial mutations. Moreover, it provides evidence supporting AE as a tool for mtDNA disease research with implications in development of DNA-based therapeutics.

scholarly journals Mitochondrial function and increased convective O2 transport: implications for the assessment of mitochondrial respiration in vivo

2013 ◽  
Vol 115 (6) ◽  
pp. 803-811 ◽  
Author(s):  
Gwenael Layec ◽  
Luke J. Haseler ◽  
Joel D. Trinity ◽  
Corey R. Hart ◽  
Xin Liu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Near Infrared ◽  
Reactive Hyperemia ◽  
Atp Synthesis ◽  
Synthesis Rate ◽  
Resonance Spectroscopy ◽  
Doppler Ultrasound Imaging

Although phosphorus magnetic resonance spectroscopy (31P-MRS)-based evidence suggests that in vivo peak mitochondrial respiration rate in young untrained adults is limited by the intrinsic mitochondrial capacity of ATP synthesis, it remains unknown whether a large, locally targeted increase in convective O2 delivery would alter this interpretation. Consequently, we examined the effect of superimposing reactive hyperemia (RH), induced by a period of brief ischemia during the last minute of exercise, on oxygen delivery and mitochondrial function in the calf muscle of nine young adults compared with free-flow conditions (FF). To this aim, we used an integrative experimental approach combining 31P-MRS, Doppler ultrasound imaging, and near-infrared spectroscopy. Limb blood flow [area under the curve (AUC), 1.4 ± 0.8 liters in FF and 2.5 ± 0.3 liters in RH, P < 0.01] and convective O2 delivery (AUC, 0.30 ± 0.16 liters in FF and 0.54 ± 0.05 liters in RH, P < 0.01), were significantly increased in RH compared with FF. RH was also associated with significantly higher capillary blood flow ( P < 0.05) and faster tissue reoxygenation mean response times (70 ± 15 s in FF and 24 ± 15 s in RH, P < 0.05). This resulted in a 43% increase in estimated peak mitochondrial ATP synthesis rate (29 ± 13 mM/min in FF and 41 ± 14 mM/min in RH, P < 0.05) whereas the phosphocreatine (PCr) recovery time constant in RH was not significantly different ( P = 0.22). This comprehensive assessment of local skeletal muscle O2 availability and utilization in untrained subjects reveals that mitochondrial function, assessed in vivo by 31P-MRS, is limited by convective O2 delivery rather than an intrinsic mitochondrial limitation.

Force, speed, and oxygen consumption in Thoroughbred and draft horses

1998 ◽  
Vol 84 (6) ◽  
pp. 2052-2059 ◽  
Author(s):  
U. Silke Birlenbach Potard ◽  
David E. Leith ◽  
M. Roger Fedde
Keyword(s):  
Body Weight ◽  
Oxygen Consumption ◽  
High Intensity ◽  
High Intensity Exercise ◽  
Peak Efficiency ◽  
Exercise Tests ◽  
Progressive Exercise ◽  
Draft Force ◽  
External Power ◽  
Locomotor Muscles

Thoroughbred (TB) and draft horses (DH) have long been selected for tasks of very different intensities and force-speed relationships. To study their adaptations, we measured O2 consumption and related variables in three TB and four DH during progressive exercise tests on a level treadmill. The horses exerted a draft force of 0, 5, 10, 15, or 20% of their body weight at speeds that increased by 2 m/s every 3 min until they could not maintain that speed. We found that TB could exert the same draft forces as DH and, at each force, TB achieved about twice the speed, twice the external power, and twice the O2 consumption as DH; thus the two breeds had the same gross efficiencies. We also found maximal O2 consumption of TB to be about twice that of DH (134 vs. 72 ml ⋅ kg−1 ⋅ min−1, respectively), suggesting adaptations to high-intensity exercise. Peak efficiency was reached at lower speeds in DH than in TB, suggesting adaptations to high-force, low-speed exercise. These differences between TB and DH in force-speed and aerobic capacities and in speed for peak efficiency likely reflect different contraction velocities in locomotor muscles.

Caffeine, performance, and metabolism during repeated Wingate exercise tests

1998 ◽  
Vol 85 (4) ◽  
pp. 1502-1508 ◽  
Author(s):  
F. Greer ◽  
C. McLean ◽  
T. E. Graham
Keyword(s):  
Power Output ◽  
High Intensity ◽  
Anaerobic Metabolism ◽  
Exercise Bout ◽  
High Intensity Exercise ◽  
Intense Exercise ◽  
Short Term ◽  
Exercise Tests ◽  
Negative Effect ◽  
Epinephrine Concentration

Investigations examining the ergogenic and metabolic influence of caffeine during short-term high-intensity exercise are few in number and have produced inconsistent results. This study examined the effects of caffeine on repeated bouts of high-intensity exercise in recreationally active men. Subjects ( n = 9) completed four 30-s Wingate (WG) sprints with 4 min of rest between each exercise bout on two separate occasions. One hour before exercise, either placebo (Pl; dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did not have any effect on power output (peak or average) in the first two WG tests and had a negative effect in the latter two exercise bouts. Plasma epinephrine concentration was significantly increased 60 min after Caf ingestion compared with Pl; however, this treatment effect disappeared once exercise began. Caf ingestion had no significant effect on blood lactate, O2 consumption, or aerobic contribution at any time during the protocol. After the second Wingate test, plasma NH3concentration increased significantly from the previous WG test and was significantly higher in the Caf trial compared with Pl. These data demonstrate no ergogenic effect of caffeine on power output during repeated bouts of short-term, intense exercise. Furthermore, there was no indication of increased anaerobic metabolism after Caf ingestion with the exception of an increase in NH3 concentration.

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