Conjard A, Ferrier B, Martin M, Caillette A, Carrier H, Baverel G
Laboratoire de Physiopathologie Métabolique et Rénale (INSERM C.R.I. 95-02-01), Faculté de Médecine Alexis Carrel, Lyon, France.
J Am Soc Nephrol. 1995 Jul;6(1):68-74. doi: 10.1681/ASN.V6168.
In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.
为了增进对慢性肾衰竭患者骨骼肌中最近观察到的能量代谢改变潜在机制的了解，本研究旨在测试：（1）这些患者肌肉中能量代谢关键酶的活性是否发生变化；如果发生变化，（2）不同肌纤维类型的代谢机制是否同样发生改变。为此，在从7名正常受试者和7名终末期肾衰竭患者肾替代治疗前获取的腹直肌活检组织中显微解剖得到的单个肌纤维中，测量了14种酶的最大活性。在三种纤维类型（慢肌氧化型、快肌氧化-糖酵解型和快肌糖酵解型）中，观察到β-氧化途径的关键酶β-羟酰基辅酶A脱氢酶、启动三羧酸循环的柠檬酸合酶以及有助于从乳酸合成糖原的果糖-1,6-二磷酸酶的活性大幅下降。在慢肌氧化型和/或快肌氧化-糖酵解型纤维中，还观察到糖酵解的两种关键酶磷酸果糖激酶和/或丙酮酸激酶的活性有较小程度的降低。这些结果表明，慢性肾衰竭患者中观察到的肌肉能量代谢异常至少部分归因于主要供能途径关键酶的内在变化；它们也为最近在这些患者肌肉中证实的氧化代谢缺陷提供了令人满意的解释。
