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Fig 1.

Exercise performance of control and BDK-mKO mice.

(A) Running distance to exhaustion before and after 2 weeks of training, and (B) swimming time to exhaustion of untrained mice on each of 4 consecutive days. # Significant difference between control and BDK-mKO mice.

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Fig 1 Expand

Fig 2.

Plasma BCAA concentrations of control and BDK-mKO mice with and without the running exercise bout.

# Significant difference between control and BDK-mKO mice. * Significant difference in the same group of mice with and without the exercise bout.

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Fig 2 Expand

Fig 3.

Glycogen contents in skeletal muscle of control and BDK-mKO mice with and without the exercise bout.

# Significant difference between control and BDK-mKO mice. * Significant difference in the same group of mice with and without the exercise bout.

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Fig 3 Expand

Fig 4.

BCAAs and their metabolites.

Changes in the metabolite levels in the skeletal muscle of control and BDK-mKO mice with and without the exercise bout are shown. # Significant difference between control and BDK-mKO mice. * Significant difference in the same group of mice with and without the exercise bout. PMP, pyridoxamine 5'-phosphate; KIC, α-ketoisocaproate; KMV, α-keto-ß-methylvalerate; KIV, α-ketoisovalerate; ßMB-CAR, ß-methylbutyryl-carnitine; αMB-CAR, α-methylbutyryl-carnitine; IB-CAR, isobutyryl-carnitine; and αKG, α-ketoglutarate.

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Fig 4 Expand

Fig 5.

Metabolites in the glycolytic pathway.

Changes in metabolite levels in skeletal muscle of BDK-mKO mice and control mice with and without the exercise bout are shown. # Significant difference between control and BDK-mKO mice. G6P, glucose 6-phosphate; F1,6BP, fructose 1,6-bisphosphate; DHAP, dihydroxyacetone phosphate; 2PG, 2-phosphoglycerate; and PEP, phosphoenolpyruvate.

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Fig 5 Expand

Fig 6.

Acetyl-CoA and metabolites in the TCA cycle.

Changes in metabolite levels in skeletal muscle of BDK-mKO mice and control mice with and without the exercise bout are shown. # Significant difference between control and BDK-mKO mice. * Significant difference in the same group of mice with and without exercise bout. αKG, α-ketoglutarate.

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Fig 6 Expand

Fig 7.

NADH, NAD+, and high energy compounds.

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Fig 7 Expand

Fig 8.

Citrate synthase and cytochrome c oxidase activities.

# Significant difference between control and BDK-mKO mice.

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Fig 8 Expand

Fig 9.

A schematic model of the perturbation of energy metabolism in association with enhanced BCAA catabolism.

The low levels of muscle glycogen in BDK-mKO mice may lead to decreased levels of some metabolites in the glycolytic pathway. Accelerated decarboxylation of BCKAs promotes transamination of BCAAs, resulting in the production of Glu. The increased Glu may contribute to the production of Asp and Ala from oxaloacetate (OA) and pyruvate (Pyr), respectively, which may be responsible for the low levels of acetyl-CoA, citrate, and isocitrate in the muscle of BDK-mKO mice. On the other hand, accelerated decarboxylation of BCKAs produces acyl-CoAs, which appear to be converted mainly to acyl-carnitines (acyl-CARs). F1,6BP, fructose 1,6-bisphosphate; 2PG, 2-phosphoglycerate; PEP, phosphoenolpyruvate; and αKG, α-ketoglutarate.

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Fig 9 Expand