Pyruvate dehydrogenase activity and acetyl group accumulation during exercise after different diets

Abstract

Pyruvate dehydrogenase activity (PDHa) and acetyl group accumulation were examined in human skeletal muscle at rest and during exercise after different diets. Five males cycled at 75% of maximal O2 uptake (VO2 max) to exhaustion after consuming a low-carbohydrate diet (LCD) for 3 days and again 1-2 wk later for the same duration after consuming a high-carbohydrate diet (HCD) for 3 days. Resting PDHa was lower after a LCD (0.20 +/- 0.04 vs. 0.69 +/- 0.05 mmol.min-1.kg wet wt-1; P < 0.05) and coincided with a greater intramuscular acetyl-CoA-to-CoASH ratio, acetyl-CoA content, and acetylcarnitine content. PDHa increased during exercise in both conditions but at a lower rate in the LCD condition compared with the HCD condition (1.46 +/- 0.25 vs. 2.65 +/- 0.23 mmol.min-1.kg wet wt-1 at 16 min and 1.88 +/- 0.20 vs. 3.11 +/- 0.14 at the end of exercise; P < 0.05). During exercise muscle acetyl-CoA and acetylcarnitine content and the acetyl-CoA-to-CoASH ratio decreased in the LCD condition but increased in the HCD condition. Under resting conditions PDHa was influenced by the availability of fat or carbohydrate fuels acting through changes in the acetyl-CoA-to-CoASH ratio. However, during exercise the activation of PDHa occurred independent of changes in the acetyl-CoA-to-CoASH ratio, suggesting that other factors are more important.

Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

“…AcCoA, acetyl-CoA; MaCoA, malonyl-CoA; FACoA, fatty acyl-CoA; CAT, carnitine acetyltransferase; CPT, carnitine palmitoyltransferase-1/2 system; AMPK, 5Ј-AMP-activated protein kinase; CL, citrate lyase; ϩ, activating effect; Ϭ, inhibiting effect. muscle carnitine content and fat oxidation rate were markedly higher with low muscle glycogen (25). Taken together, the present and previous studies suggest a relation between muscle free carnitine availability and fat oxidation rate in human skeletal muscle during exercise.…”

“…The combination of unchanged free carnitine content and reduced malonyl-CoA content leads to a marked increase in fat oxidation rate from rest to exercise. Muscle concentration of pyruvate was not measured in the present study but was previously shown to increase more from rest to exercise with high than with low muscle glycogen (25). The muscle concentration of citrate, the source of the acetyl-CoA from which malonyl-CoA is generated (35), was not measured in the present study but was previously shown not to differ during exercise with high and low muscle glycogen, although an increase with exercise occurred (11).…”

“…The frozen muscle tissue (10 mg) was homogenized in 300 l of buffer (pH 7.8) containing 200 mM sucrose, 50 mM KCl, 5 mM MgCl2, 5 mM EGTA, 50 mM Tris ⅐ HCl, 50 mM NaF, 5 mM dichloroacetate, and 0.1% Triton X-100. Subsequently, PDHa activity was determined by a radioisotopic assay first described by ConstantinTeodosiu et al (6) and modified by Putman et al (25). The CV between five single determinations on the same muscle extract was 17%, and the CV between four different muscle extracts from the same biopsy determined in duplicate was 17%.…”

The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity

“…Many models have been used to perturb this partitioning, such as starvation (12,17,26,36), and a high-fat diet (27,28,30). One such perturbation previously used has been endurance training (17,19,20), which in general causes a shift toward increased fat oxidation and decreased carbohydrate utilization.…”

“…It has been found that in states of restricted carbohydrate availability there is an increase in skeletal muscle PDK activity (5,6,26,27,28) and PDK4 protein content (26,27,36), while similar nutritional states also cause a decrease in PDP2 protein content in rat heart and kidney (12) and skeletal muscle, with this decrease leading to a decrease in PDP activity (17). As a result of these adaptations there is an overall decrease in the active form of PDH (PDHa; 6,28,30), allowing for the conservation of carbohydrates, which is essential during these carbohydratedeficient perturbations.…”