Effects of acetate infusion and hyperoxia on muscle substrate phosphorylation after onset of moderate exercise

Abstract

This study investigated whether increased muscle acetylcarnitine provision (acetate infusion) or hyperoxia (100% O(2)) would increase the rate of oxidative phosphorylation and reduce the reliance on muscle substrate phosphorylation after the onset of moderate exercise. Eight subjects completed three randomized trials, each separated by 1 wk: 1) saline infusion for 1 h before exercise, while breathing room air for 20 min before exercise and during 120 s of cycling at 65% maximal exercise (VO(2 max)) (CON), 2) saline infusion with 4 mmol/kg body wt sodium acetate, while breathing room air before and during exercise (ACE), and 3) saline infusion and breathing 100% O(2) before and during exercise (HYP). Muscle biopsies were sampled at rest and after 30 and 120 s of exercise. ACE increased muscle acetyl-CoA and acetylcarnitine contents at rest vs. CON and HYP [22.9 +/- 2.8 vs. 8.9 +/- 2.4 and 10.5 +/- 1.8 micromol/kg dry muscle (dm); 11.0 +/- 1.2 vs. 3.5 +/- 1.3 and 4.0 +/- 1.2 mmol/kg dm]. Acetate had no effect on resting pyruvate dehydrogenase activity in the active form (PDH(a)) among CON, ACE, and HYP. During exercise, acetyl-CoA and acetylcarnitine were unchanged in ACE but increased over time in the CON and HYP trials, and PDH(a) increased similarly in all trials. Muscle phosphocreatine use, lactate accumulation, and substrate phosphorylation energy provision after 30 or 120 s of exercise were similar in all trials. In summary, increased acetylcarnitine availability did not accelerate the rate of oxidative phosphorylation at the onset of exercise, suggesting that this is not a site of extra substrate. Hyperoxia had no effect on substrate phosphorylation, suggesting that O(2) availability does not limit oxidative phosphorylation at the onset of moderate exercise.

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

“…The dose of acetate used in the present study has been shown previously to near maximally acetylate carnitine and free CoASH pools in human skeletal muscle at rest (7,17,25).…”

“…Studies that have investigated acetyl group utilization during moderate-to-intense skeletal muscle contraction after sodium acetate pretreatment have reported no reduction in the requirement for oxygen-independent ATP production at any contraction time point (7,17,25), implying that elevating acetyl group availability, independently of PDC activation, cannot overcome the period of metabolic inertia and thereby accelerate the onset of mitochondrial ATP production. These previous findings are rather at odds with those reported in the present study; however, this lack of concordance can be accounted for, and on several levels.…”

“…In particular, we wished to investigate the time course of PDC activation, acetyl group accumulation, substrate utilization, and tension development during 5 min of electrically evoked ischemic muscular contraction. This was done in the absence and presence of pretreatment with sodium acetate, a known PDC independent acetylator of muscle carnitine and free CoASH pools (7,17,25).…”

The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle

“…Therefore, at workloads above this intensity, pretreatment with DCA is unlikely to be associated with a reduction in ATP resynthesis from SLP and an improvement in contractile function. Similarly, based on the findings of Howlett et al (1999) outlined above and the more recent findings of Evans et al (2001), we would propose that there will also be a lower exercise intensity below which acetyl group delivery via the PDC reaction is not limiting towards TCA cycle demands (i.e. where PDC flux and/or fat-mediated acetyl group delivery is sufficient to match the energy demands of contraction).…”

“…Presumably this exercise intensity equates to one where no increase or decline in acetylcarnitine concentration would be seen upon the initiation of exercise. In this respect, the study by Evans et al (2001) investigated changes in acetyl group availability during 2 min of moderate-intensity (65 % ◊ O 2,max ) exercise in human volunteers following near maximal acetylation of the muscle carnitine and CoASH pools by sodium acetate infusion. In line with our proposal, no changes in acetyl-CoA or acetylcarnitine concentrations were observed following 30 s of exercise in either saline-(control) or sodium acetate-treated subjects, despite the PDC activation that occurred in both groups.…”