Acetate Metabolism during Hemodialysis: Metabolic Considerations

Vinay, Patrick; Cardoso, Manuel; Tejedor, Alberto; Prudhomme, Michel; Levelillee, Michel; Vinet, Bernard; Courteau, Maryse; Gougoux, A.; Rengel, M.; Lapierre, Louis R.; Piette, Yves

doi:10.1159/000167500

Cited by 41 publications

(18 citation statements)

References 55 publications

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“…4; Ref. 38). The increased available acetic acid, from the action of acetyl-CoA synthase and consumption of ATP, is converted into acetyl-CoA in the cytosol of the muscle cell ( Fig.…”

Section: Discussionmentioning

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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“…4; Ref. 38). The increased available acetic acid, from the action of acetyl-CoA synthase and consumption of ATP, is converted into acetyl-CoA in the cytosol of the muscle cell ( Fig.…”

Section: Discussionmentioning

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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“…This fall in Pa,O 2 may not be tolerated by patients with chronic renal failure who may also have cardiopulmonary disease [13]. Supplemental oxygen therapy may be required to correct the hypoxaemia [1,[14][15].…”

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confidence: 99%

Effect of oxygen on breathing irregularities during haemodialysis in patients with chronic uraemia

Yap¹,

Wang²,

Poh³

1998

Eur Respir J

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Hypoxaemia and breathing irregularities have been shown to occur during haemodialysis in patients with chronic renal failure. This study examined the role of hypoxia in the genesis of the irregular breathing during haemodialysis. The ventilatory patterns using respiratory inductance plethysmography and arterial blood gases were studied in seven males with chronic renal failure on long-term haemodialysis. The study was carried out before and during dialysis on one day without (D1) and another day with intranasal oxygen at 4 L x min(-1) (D2). On D1, mean (SD) arterial oxygen tension (Pa,O2) fell 1.9 (0.9) kPa (p<0.001) and mean minute ventilation (V'E) fell 1.9 (1.1) L x min(-1) (p<0.01) during dialysis. The arterial carbon dioxide tension (Pa,CO2) did not show a significant decrease (4.7 (0.2) kPa before and 4.6 (0.2) kPa during dialysis). Cumulative number of apnoeas was 64 and the coefficients of variation (COV) of respiratory frequency (fR) and tidal volume (VT) were 29.6 (11.9) and 38.2 (11.9)%, respectively. On D2, mean Pa,O2 remained stable (20.4 (4.1) kPa before, 21.3 (4.1) kPa during dialysis). There was no significant change in mean V'E (6.4 (0.9) L x min(-1) before, 5.5 (0.5) L x min(-1) during dialysis). Pa,CO2 decrease was not significant but the fall was greater (4.8 (0.1) kPa before, 45 (0.5) kPa during dialysis). Cumulative number of apnoeas was 94 and the COVs offR and VT were 35.8 (5.1) and 40.5 (11.3)%, respectively. Oxygen administration did not significantly affect the haemodialysis-induced changes in ventilation and breathing pattern, despite a significant protective effect from the fall in arterial oxygen tension. It was concluded that the fall in arterial oxygen tension is not the main determinant of breathing irregularities during haemodialysis.

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“…In this instance the equilibrium reaction depicted in Fig. 1 would shift markedly to the left following bicarbonate administration; however, due to the rapid removal of acetic acid by the muscle mass (Vmm = 300 mmol h-'; Vinay et al 1987), a considerable back pressure would exist to produce acetic acid and reset the equilibrium, thereby driving cellular acetyl group accumulation ( Fig. 1; Vinay et al 1987).…”

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confidence: 96%

“…1 would shift markedly to the left following bicarbonate administration; however, due to the rapid removal of acetic acid by the muscle mass (Vmm = 300 mmol h-'; Vinay et al 1987), a considerable back pressure would exist to produce acetic acid and reset the equilibrium, thereby driving cellular acetyl group accumulation ( Fig. 1; Vinay et al 1987). Assuming this occurs, and that the bicarbonate-induced augmentation of acetyl-CoA availability is of sufficient magnitude, it could potentially overcome the period of metabolic inertia during the rest-to-work transition (Roberts et al 2000), reduce ATP production from nonoxygen-dependent routes and lead to an improvement in contractile function in a manner not dissimilar to dichloroacetate and sodium acetate pre-treatment (Roberts et al 2000,2001 …”

mentioning

confidence: 99%

Bicarbonate‐induced alkalosis augments cellular acetyl group availability and isometric force during the rest‐to‐work transition in canine skeletal muscle

Roberts

Loxham

Poucher

et al. 2002

Experimental Physiology

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Increasing blood bicarbonate content has long been cited as a potential mechanism to improve contractile function. We investigated whether sodium bicarbonate-induced metabolic alkalosis could positively affect force development during the rest-to-work transition in ischaemic skeletal muscle. Secondly, assuming it could, we investigated whether bicarbonate could augment acetyl group availability through the same equilibrium reaction as sodium acetate pre-treatment and whether this underpins, at least in part, its ergogenic effect. Multiple biopsy samples were obtained from the canine gracilis muscle during 5 min of electrically evoked ischaemic Contraction, which enabled the determination of the time course of acetyl group accumulation, substrate utilisation, pyruvate dehydrogenase complex activation and tension development in animals treated with saline (control; n = 6 ) or sodium bicarbonate (n=5). Treatment with bicarbonate elevated acetylcarnitine content above the control level at rest ( P < 0.03, but at no time point during subsequent contraction. The pyruvate dehydrogenase complex was activated following 40 s of contraction in both groups, with no differences existing between treatments at any time point. The requirement for ATP resynthesis from non-oxygen-dependent routes was no different between groups at any time point during contraction. No difference in peak twitch force production existed between groups. However, at 3 min of stimulation, tension development was better maintained in the bicarbonate group (P < 0.05), being -20% greater than control following 5 rnin of contraction (P < 0.05). The results demonstrate, for the first time, that bicarbonate can augment acetyl group availability prior to contraction, independent of pyruvate dehydrogenase complex activation, but cannot influence the requirement for non-oxidative ATP re-synthesis during subsequent contraction. It would appear, therefore, that the bicarbonate-induced improvement in muscle tension development was probably mediated through the metabolic alkalosis and not via the increased availability of acetyl groups within the cell. Experimental Physiologv (2002) 87.4,489498. At the onset of skeletal muscle contraction there is substantial reliance upon ATP re-synthesis from nonoxygen-dependent routes (i.e. ATP and phosphocreatine (PCr) hydrolysis and glycolysis), frequently termed substrate level phosphorylation, to meet the increased energy demand of work, which cannot be met solely via mitochondrial ATP re-synthesis (for review see Greenhaff & Timmons, 1998; Tschakovsky & Hughson, 1999). Although ATP production from substrate level phosphorylation enables rapid rates of ATP turnover to be achieved, it has only a finite capacity and also results in the accumulation of metabolites that are deleterious to muscle function (hydrogen ions, lactate ions and inorganic phosphate)

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Acetate Metabolism during Hemodialysis: Metabolic Considerations

Cited by 41 publications

References 55 publications

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

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

Effect of oxygen on breathing irregularities during haemodialysis in patients with chronic uraemia

Bicarbonate‐induced alkalosis augments cellular acetyl group availability and isometric force during the rest‐to‐work transition in canine skeletal muscle

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