Increased acetyl group availability enhances contractile function of canine skeletal muscle during ischemia.

Timmons, James A.; Poucher, Simon M.; Constantin‐Teodosiu, Dumitru; Worrall, V; Macdonald, I. A.; Greenhaff, Paul L.

doi:10.1172/jci118490

Cited by 73 publications

(121 citation statements)

References 28 publications

(30 reference statements)

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“…However, Gibala, MacLean, Graham & Saltin, (1998) Dichloroacetate infusion results in near-maximal activation of the pyruvate dehydrogenase complex and stockpiling of acetyl-units. During the transition to subsequent moderate intensity exercise, dichloroacetate infusion has consistently been shown to enhance the rate of increase of oxidative metabolism as indicated by a reduction in phosphocreatine degradation and lactate accumulation (Timmons et al 1996;Timmons, Poucher, Constantin-Teodosiu, Macdonald & Greenhaff, 1997;Timmons et al 1998aTimmons, Gustafsson, Sundberg, Jansson & Greenhaff, 1998bHowlett, Heigenhauser, Hultman, Hollidge-Horvat & Spriet, 1999a;Parolin et al 2000;Roberts, Loxham, Poucher, Constantin-Teodosiu & Greenhaff, 2002).…”

Section: Introductionmentioning

confidence: 99%

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise

Marwood

Bowtell

2008

Journal of Sports Sciences

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Glutamine enhances the exercise-induced expansion of the tricarboxylic acid intermediate pool. The aim of the present study was to determine whether oral glutamine, alone or in combination with hyperoxia, influenced oxidative metabolism and cycle time-trial performance. 8 participants consumed either placebo or 0.125g.kg body mass -1 of glutamine in 5 ml.kg body mass -1 placebo 1 h prior to exercise in normoxic (control & glutamine respectively) or hyperoxic (FiO 2 =50%;hyperoxia & hyperoxia and glutamine respectively) conditions. Participants then cycled for 6 min at 70% 2 o V  max immediately before completing a brief high intensity time-trial (~ 4min) where a pre-determined volume of work was completed as fast as possible. The increment in pulmonary oxygen uptake during the performance test ( 2 o V  , p=0.02) and exercise performance {243  7 (control) vs 242  3 (glutamine) vs 231  3 (hyperoxia) vs 228  5 (hyperoxia and glutamine) s, p<0.01} were significantly improved in hyperoxic conditions. There was some evidence that glutamine ingestion increased  2 o V  in normoxia, but not hyperoxia (interaction drink/FiO 2 , p=0.04) however there was no main effect or impact on performance. Overall the present data show no effect of glutamine ingestion either alone or in combination with hyperoxia, and thus no limiting effect of the tricarboxylic acid intermediate pool size, on oxidative metabolism and performance during maximal exercise.

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Section: Introductionmentioning

confidence: 99%

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise

Marwood

Bowtell

2008

Journal of Sports Sciences

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“…Classically, the lag in oxidative ATP production and resulting oxygen deficit have been attributed to a lag in muscle blood flow and thereby muscle oxygen delivery, which also follows an approximately exponential time course (21, 30). However, more recently it has been proposed that oxygen availability may not be the sole determinant of the oxygen deficit, at least at submaximal exercise workloads (11,29), such that the delay in mitochondrial energy production must be attributable, at least in part, to a lag in enzyme activation and/or substrate delivery (metabolic inertia) within energy-producing pathways on the initiation of muscular contraction (10,12,18,37).A recent series of studies by our group has demonstrated the existence of metabolic inertia at the onset of contraction (27,28,(33)(34)(35)(36). On the basis of evidence from these studies, we believe that the delay in acetyl-CoA provision at the onset of exercise, which we have termed the "acetyl group deficit" (27), is a principal determinant of the oxygen deficit (27,33,34).…”

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confidence: 99%

Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle

Roberts

Loxham²,

Poucher³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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-We examined the effects of increasing acetylcarnitine and acetyl-CoA availability at rest, independent of pyruvate dehydrogenase complex (PDC) activation, on energy production and tension development during the rest-to-work transition in canine skeletal muscle. We aimed to elucidate whether the lag in PDC-derived acetyl-CoA delivery toward the TCA cycle at the onset of exercise can be overcome by increasing acetyl group availability independently of PDC activation or is intimately dependent on PDCderived acetyl-CoA. Gracilis muscle pretreated with saline or sodium acetate (360 mg/kg body mass) (both n ϭ 6) was sampled repeatedly during 5 min of ischemic contraction. Acetate increased acetylcarnitine and acetyl-CoA availability (both P Ͻ 0.01) above control at rest and throughout contraction (P Ͻ 0.05), independently of differences in resting PDC activation between treatments. Acetate reduced oxygen-independent ATP resynthesis ϳ40% (P Ͻ 0.05) during the first minute of contraction. No difference in oxygen-independent ATP resynthesis existed between treatments from 1 to 3 min of contraction; however, energy production via this route increased ϳ25% (P Ͻ 0.05) above control in the acetate-treated group during the final 2 min of contraction. Tension development was ϳ20% greater after 5-min contraction after acetate treatment than in control (P Ͻ 0.05). In conclusion, at the immediate onset of contraction, when PDC was largely inactive, increasing cellular acetyl group availability overcame inertia in mitochondrial ATP regeneration. However, after the first minute, when PDC was near maximally activated in both groups, it appears that PDC-derived acetyl-CoA, rather than increased cellular acetyl group availability per se, dictated mitochondrial ATP resynthesis.acetylcarnitine; oxygen deficit; oxidative phosphorylation; phosphocreatine; sodium acetate THE READJUSTMENT of oxidative (mitochondrial) ATP production to meet the increase in muscular energy demand during the transition from rest to exercise, or the step increase from one workload to another, is delayed and follows an approximately exponential time course (for review, see Ref. 37). During this period of latency, the transient shortfall in mitochondrial ATP production, classically termed the "oxygen deficit" (21, 30), is supplemented by ATP resynthesis from non-oxygen-dependent routes [i.e., ATP and phosphocreatine (PCr) breakdown and glycolysis]. Although ATP production from oxygen-independent routes enables rapid rates of ATP turnover to be achieved, it has only a finite capacity and also results in the accumulation of metabolic byproducts that are deleterious to muscular contractile function (hydrogen ions, lactate ions, and inorganic phosphate; see Ref. 8). Indeed, without the progressive increase in mitochondrial ATP production at the onset of contraction, the onset of muscular fatigue would be markedly accelerated. Classically, the lag in oxidative ATP production and resulting oxygen deficit have been attributed to a lag in muscle blood flow and thereby m...

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“…Muscle [ATP], [PCr], and lactate efflux during the I condition were not significantly different from the values seen at the same stimulation intensity with normal blood flow. Timmons et al (29) found muscle [PCr] and [ATP] to be significantly more depleted (and found greater lactate accumulation) in contracting muscle when partial ischemia was imposed from the onset of contractions compared with a control condition at the same stimulation frequency but with normal blood flow. It is likely that in the present study, the lack of any significant differences in muscle [PCr], [ATP], and lactate efflux beween the I condition and the same stimulation with normal blood flow was due to the fact that the muscle was in a steady state of contractile activity, with all regulatory enyzmes fully activated, when the partial ischemia was induced.…”

Section: Skeletal Muscle Bioenergetics After Blood Flow Reductionmentioning

confidence: 99%

“…Timmons et al (28)(29)(30) recently demonstrated that substrate availability through the pyruvate dehydrogenase complex (PDC) for carbohydrate oxidation in the tricarboxylic cycle can affect subsequent muscle performance during moderate ischemia. These investigators (30) demonstrated that having the PDC enzyme fully activated at the onset of an ischemic contractile period resulted in significantly less PCr hydrolysis and lactate accumulation and subsequently less fatigue compared with the same ischemic blood flow reduction with PDC starting from the normal resting deactivated state.…”

mentioning

confidence: 99%

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

Hogan

Gladden

Grassi

et al. 1998

Journal of Applied Physiology

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Hogan, Michael C., L. Bruce Gladden, Bruno Grassi, Creed M. Stary, and Michele Samaja. Bioenergetics of contracting skeletal muscle after partial reduction of blood flow. J. Appl. Physiol. 84(6): 1882-1888, 1998.-The purpose of this study was to examine the bioenergetics and regulation of O 2 uptake (V O 2 ) and force production in contracting muscle when blood flow was moderately reduced during a steadystate contractile period. Canine gastrocnemius muscle (n ϭ 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic (I) condition] to 46 Ϯ 3% of the value obtained at 0.5 Hz with normal blood flow. The V O 2 of the contracting muscle was significantly (P Ͻ 0.05) reduced during the I condition [6.5 Ϯ 0.8 (SE) ml · 100 g Ϫ1 · min Ϫ1 ] compared with the same stimulation frequency with normal flow (11.2 Ϯ 1.5 ml · 100 g Ϫ1 · min Ϫ1 ), as was the tension-time index (79 Ϯ 12 vs. 123 Ϯ 22 N·g Ϫ1 · min Ϫ1 , respectively). The ratio of V O 2 to tension-time index remained constant throughout all contraction periods. Muscle phosphocreatine concentration, ATP concentration, and lactate efflux were not significantly different during the I condition compared with the 0.5-Hz condition with normal blood flow. However, at comparable rates of V O 2 and tension-time index, muscle phosphocreatine concentration and ATP concentration were significantly less during the I condition compared with normal-flow conditions. These results demonstrate that, in this highly oxidative muscle, the normal balance of O 2 supply to force output was maintained during moderate ischemia by downregulation of force production. In addition, 1) the minimal disruption in intracellular homeostasis after the initiation of ischemia was likely a result of steady-state metabolic conditions having already been activated, and 2) the difference in intracellular conditions at comparable rates of V O 2 and tension-time index between the normal flow and I condition may have been due to altered intracellular O 2 tension. oxygen uptake; exercise; adenosine 5Ј-triphosphate; lactate; lactic acid; mitochondrial respiration; phosphocreatine; glycolysis IN MOST CONDITIONS of steady-state muscle contractile activity, ATP production related to the O 2 uptake (V O 2 ) of the contracting muscle is tightly coupled to the rate of ATP demand so that steady-state energy expenditure is maintained with minimal change in intracellular ATP concentration ([ATP]; e.g., see Ref. 12). When the supply of O 2 (and oxidative substrate) to the mitochondria is sufficient, increases in myofibril ATPase activity with higher energy demands result in changes in the concentration of several signals [phosphocreatine (PCr), ADP, P i , etc.] that are thought to regulate mitochondrial respiration (4,5,18,20,22) in a manner that causes oxidative phosphorylation to increase proportionally with ATPase activity. However, when the supply of O 2 to ...

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Increased acetyl group availability enhances contractile function of canine skeletal muscle during ischemia.

Cited by 73 publications

References 28 publications

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise

Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

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