Exercise with low muscle glycogen augments TCA cycle anaplerosis but impairs oxidative energy provision in humans

We tested the hypotheses that: (i) exercise with low muscle glycogen would reduce pyruvate flux through the alanine aminotransferase (AAT) reaction and attenuate the increase in tricarboxylic acid (TCA) cycle intermediates, and (ii) attenuation of tricarboxylic acid cycle intermediate (TCAI) pool expansion would limit TCA cycle flux, thereby accelerating phosphocreatine (PCr) degradation. Eight men cycled for 10 nun at 70% of their V-O2,V-max on two occasions: (i) following their normal diet (CON) and (ii) after cycling to exhaustion and consuming a low carbohydrate diet for similar to2 days (LG). Biopsies (m. vastus lateralis) confirmed that [glycogen] was lower in LG vs. CON at rest (257 18 vs. 611 +/- 54 mmol (kg dry mass)(-1); P < 0.05); however, net glycogenolysis was not different after 1 or 10 min of exercise. PCr degradation from rest to 1 min was similar to26% higher in LG vs. CON (38 4 vs. 28 +/- 4 mmol (kg dry mass)(-1); P less than or equal to 0.05). The sum of five measured TCAIs (similar to90% of total pool) was not different between trials at rest and after 1 min, but was higher after 10 min in LG vs. CON (5.51 +/- 0.43 vs. 4.45 +/- 0.49 mmol (kg dry mass)(-1); P less than or equal to 0.05). Pyruvate dehydrogenase complex (PDC) activity was lower during exercise in LG vs. CON (2.2 +/- 0.2 vs. 1.4 +/- 0.2 mmol min(-1) (kg wet weight)(-1) after 10 min; P less than or equal to 0.05), and acetylcarnitine was similar tothreefold less, implying increased pyruvate availability for flux through AAT. Resting muscle [glutamate] was higher in LG vs. CON (16.1 +/- 0.8 vs. 11.8 +/- 0.4 mmol (kg dry mass)(-1); P less than or equal to 0.05) and the net decrease in [glutamate] during exercise was similar to30% greater in LG vs. CON. These findings suggest that: (i) contrary to our hypotheses, LG increased anaplerosis by decreasing PDC flux and/or increasing the conversion of glutamate carbon to TCAIs, and (ii) accelerating the rate of muscle TCAI expansion did not affect oxidative energy provision during the initial phase of contraction, since changes in [TCAI] were not temporally related to PCr degradation.