Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet
Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet
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DOI：
10.1152/ajpendo.1998.275.6.e980
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发表时间：
1998-12-01
影响因子：
5.1
通讯作者：
Spriet, LL
中科院分区：
文献类型：
--
作者：
Peters, SJ;St Amand, TA;Spriet, LL
为了表征人类骨骼肌酶对低碳水化合物、高脂肪和高蛋白饮食（LCD）的适应性，研究对象在6天内摄入了由碳水化合物占总能量摄入的5%、脂肪占63%、蛋白质占33%组成的高热量饮食，与正常饮食（碳水化合物占52%、脂肪占33%、蛋白质占14%）相比。在LCD上3天和6天后分别从股外侧肌进行活检。从新鲜肌肉中提取完整的线粒体，分析丙酮酸脱氢酶（PDH）激酶、总PDH、肉毒碱棕榈酰转移酶I活性和线粒体ATP生成率（使用碳水化合物和脂肪底物）。在全肌肉匀浆上测定β -羟酰基辅酶a脱氢酶、活性PDH （PDH）和柠檬酸合成酶活性。PDH激酶（PDHK）被计算为在0.3 mM Mg2+-ATP存在下PDH失活的表观一级速率常数的绝对值。PDHK在第3天急剧上升，从0.10 +/- 0.02 min（-1）上升到0.35 +/- 0.09 min(-1)，第6天上升到0.49 +/- 0.06 min（-1）。静息PDHa活性从0.63 +/- 0.17降至0.17 +/- 0.04 mmol.min（-1）。kg(-1)，而总PDH活性没有变化。所有其他酶的活性均未受LCD的影响。总之，饮食中碳水化合物的严重缺乏加上饮食中脂肪和蛋白质的两倍增加，导致人类骨骼肌中PDHK活性迅速增加3到5倍。PDHK活性的增加降低了静止状态下活性PDH的数量，降低了碳水化合物代谢。然而，参与脂肪酸氧化的酶的活性并没有增加。
To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). beta-Hydroxyacyl CoA dehydrogenase, active PDH (PDH,), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 +/- 0.02 min(-1) to 0.35 +/- 0.09 min(-1) at 3 days and 0.49 +/- 0.06 min(-1) after 6 days. Resting PDHa activity decreased from 0.63 +/- 0.17 to 0.17 +/- 0.04 mmol.min(-1).kg(-1) after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.