TY - JOUR

T1 - Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns.

AU - Fritzen, Anette J

AU - Grunnet, Niels

AU - Quistorff, Bjørn

N1 - Keywords: Adenosine Triphosphate; Algorithms; Animals; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Energy Metabolism; Exertion; Female; Male; Mitochondria, Muscle; Muscle, Skeletal; Oxidative Phosphorylation; Oxygen Consumption; Palmitoylcarnitine; Pyruvic Acid; Rats; Rats, Wistar; Uncoupling Agents

PY - 2007

Y1 - 2007

N2 - Flux control analysis of eight reactions involved in oxidative phosphorylation of mitochondria from rat quadriceps muscle was performed under circumstances resembling in vivo conditions of carbohydrate or fatty acid oxidation. The major flux control at a respiration rate of 55% of state 3 was associated with the ADP-generating system, i.e., 0.58 +/- 0.05 with pyruvate, but significantly lower, 0.40 +/- 0.05, with palmitoyl-carnitine as substrate. The flux control coefficients of complex I, III and IV, the ATP synthase, the ATP/ADP carrier and the P(i) carrier were 0.070 +/- 0.03, 0.083 +/- 0.04, 0.054 +/- 0.01, 0.11 +/- 0.03, 0.090 +/- 0.03 and 0.026 +/- 0.01, respectively, with pyruvate as substrate. With palmitoyl-carnitine all control coefficients were significantly different, except for the P(i) carrier (i.e., 0.024 +/- 0.001, 0.036 +/- 0.01, 0.052 +/- 0.02, 0.020 +/- 0.002, 0.034 +/- 0.02 and 0.012 +/- 0.002, respectively), probably caused by the shift from NADH to FADH(2) oxidation. The sum of flux control coefficients was not significantly different from unity with pyruvate, while only 0.58 with palmitoyl-carnitine, indicating significant control contributions from the enzymes involved with the fatty acid oxidation or transport. Flux control of ADP generation was specifically tested at three different respiration rates, 30, 55 and 75% of state 3. At all respiration rates control was higher with pyruvate and pyruvate + palmitoyl-carnitine compared with palmitoyl-carnitine as substrate. Also the control was lower at 75% compared to 30% of the state 3 respiration both with pyruvate and pyruvate + palmitoyl-carnitine as substrate, suggesting that muscle respiration moves from "demand control" to "supply control" as respiration increases.

AB - Flux control analysis of eight reactions involved in oxidative phosphorylation of mitochondria from rat quadriceps muscle was performed under circumstances resembling in vivo conditions of carbohydrate or fatty acid oxidation. The major flux control at a respiration rate of 55% of state 3 was associated with the ADP-generating system, i.e., 0.58 +/- 0.05 with pyruvate, but significantly lower, 0.40 +/- 0.05, with palmitoyl-carnitine as substrate. The flux control coefficients of complex I, III and IV, the ATP synthase, the ATP/ADP carrier and the P(i) carrier were 0.070 +/- 0.03, 0.083 +/- 0.04, 0.054 +/- 0.01, 0.11 +/- 0.03, 0.090 +/- 0.03 and 0.026 +/- 0.01, respectively, with pyruvate as substrate. With palmitoyl-carnitine all control coefficients were significantly different, except for the P(i) carrier (i.e., 0.024 +/- 0.001, 0.036 +/- 0.01, 0.052 +/- 0.02, 0.020 +/- 0.002, 0.034 +/- 0.02 and 0.012 +/- 0.002, respectively), probably caused by the shift from NADH to FADH(2) oxidation. The sum of flux control coefficients was not significantly different from unity with pyruvate, while only 0.58 with palmitoyl-carnitine, indicating significant control contributions from the enzymes involved with the fatty acid oxidation or transport. Flux control of ADP generation was specifically tested at three different respiration rates, 30, 55 and 75% of state 3. At all respiration rates control was higher with pyruvate and pyruvate + palmitoyl-carnitine compared with palmitoyl-carnitine as substrate. Also the control was lower at 75% compared to 30% of the state 3 respiration both with pyruvate and pyruvate + palmitoyl-carnitine as substrate, suggesting that muscle respiration moves from "demand control" to "supply control" as respiration increases.

U2 - 10.1007/s00421-007-0544-2

DO - 10.1007/s00421-007-0544-2

M3 - Journal article

C2 - 17717681

VL - 101

SP - 679

EP - 689

JO - European Journal of Applied Physiology

JF - European Journal of Applied Physiology

SN - 1439-6319

IS - 6

ER -