Constantin-Teodosiu D, Simpson E J, Greenhaff P L
School of Biomedical Sciences, University Medical School, Queen's Medical Center, Nottingham NG7 2UH, United Kingdom.
Am J Physiol. 1999 Mar;276(3):E472-8. doi: 10.1152/ajpendo.1999.276.3.E472.
No studies have singularly investigated the relationship between pyruvate availability, pyruvate dehydrogenase complex (PDC) activation, and anaplerosis in skeletal muscle. This is surprising given the functional importance attributed to these processes in normal and disease states. We investigated the effects of changing pyruvate availability with dichloroacetate (DCA), epinephrine, and pyruvate infusions on PDC activation and accumulation of acetyl groups and tricarboxylic acid (TCA) cycle intermediates (TCAI) in human muscle. DCA increased resting PDC activity sixfold (P < 0.05) but decreased the muscle TCAI pool (mmol/kg dry muscle) from 1.174 +/- 0.042 to 0.747 +/- 0.055 (P < 0.05). This was probably a result of pyruvate being diverted to acetyl-CoA and acetylcarnitine after near-maximal activation of PDC by DCA. Conversely, neither epinephrine nor pyruvate activated PDC. However, both increased the TCAI pool (1.128 +/- 0.076 to 1.614 +/- 0.188, P < 0.05 and 1.098 +/- 0.059 to 1.385 +/- 0.114, P < 0.05, respectively) by providing a readily available pool of pyruvate for anaplerosis. These data support the hypothesis that TCAI pool expansion is principally a reflection of increased muscle pyruvate availability and, together with our previous work (J. A. Timmons, S. M. Poucher, D. Constantin-Teodosiu, V. Worrall, I. A. Macdonald, and P. L. Greenhaff. J. Clin. Invest. 97: 879-883, 1996), indicate that TCA cycle expansion may be of little functional significance to TCA cycle flux. It would appear therefore that the primary effect of DCA on oxidative ATP provision is to provide a readily available pool of acetyl groups to the TCA cycle at the onset of exercise rather than increasing TCA cycle flux by expanding the TCAI pool.
尚无研究专门探究丙酮酸可用性、丙酮酸脱氢酶复合体（PDC）激活与骨骼肌中回补反应之间的关系。鉴于这些过程在正常和疾病状态下的功能重要性，这一点令人惊讶。我们研究了用二氯乙酸（DCA）、肾上腺素和丙酮酸输注改变丙酮酸可用性对人体肌肉中PDC激活、乙酰基积累和三羧酸（TCA）循环中间体（TCAI）的影响。DCA使静息PDC活性增加了六倍（P < 0.05），但肌肉TCAI池（毫摩尔/千克干肌肉）从1.174±0.042降至0.747±0.055（P < 0.05）。这可能是由于DCA使PDC接近最大激活后，丙酮酸被转移至乙酰辅酶A和乙酰肉碱的结果。相反，肾上腺素和丙酮酸均未激活PDC。然而，二者均通过为回补反应提供现成的丙酮酸池而增加了TCAI池（分别从1.128±0.076增至1.614±0.188，P < 0.05；从1.098±0.059增至1.385±0.114，P < 0.05）。这些数据支持了以下假说，即TCAI池扩大主要反映了肌肉丙酮酸可用性的增加，并且与我们之前的研究结果（J. A. Timmons, S. M. Poucher, D. Constantin-Teodosiu, V. Worrall, I. A. Macdonald, and P. L. Greenhaff. J. Clin. Invest. 97: 879 - 883, 1996）共同表明，TCA循环扩大对TCA循环通量可能几乎没有功能意义。因此，似乎DCA对氧化ATP供应的主要作用是在运动开始时为TCA循环提供现成的乙酰基池，而不是通过扩大TCAI池来增加TCA循环通量。
