ACTIVE AND INACTIVE FORMS OF PYRUVATE DEHYDROGENASE IN RAT HEART AND KIDNEY - EFFECT OF DIABETES, FASTING, AND REFEEDING ON PYRUVATE DEHYDROGENASE INTERCONVERSION
ACTIVE AND INACTIVE FORMS OF PYRUVATE DEHYDROGENASE IN RAT HEART AND KIDNEY - EFFECT OF DIABETES, FASTING, AND REFEEDING ON PYRUVATE DEHYDROGENASE INTERCONVERSION
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DOI：
10.1016/0003-9861(71)90244-x
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发表时间：
1971-01-01
影响因子：
3.9
通讯作者：
WINTON, B
中科院分区：
文献类型：
--
作者：
SIESS, OW;SCHULZEW.FH;WINTON, B
测定大鼠心脏和肾脏匀浆中丙酮酸脱氢酶（PDH）的活性。在匀浆中加入Mg2+之前的活性被用来衡量最初存在的活性形式（PDHa）。在Mg2+存在下孵育后的活性代表了组织中存在的总PDH活性。如果假设Mg2+刺激PDH磷酸酶，催化非活性PDH （PDHb）转化为活性PDH，则该试验是合理的。在经受各种代谢条件和治疗的大鼠的心脏和肾脏中观察到PDH的量有显著变化，但总PDH活性没有显著变化：禁食时PDH水平下降到总活性的15%以下。再喂葡萄糖或果糖后，pdhali水平恢复正常（占总活性的70%）。同样，四氧嘧啶型糖尿病大鼠在停止胰岛素治疗后，心脏和肾脏的pdhali水平降至总活性的15%以下，在胰岛素治疗后也恢复到正常水平。用抗脂剂烟酸治疗禁食大鼠，使禁食后降低的pdhali水平恢复正常。PDH活性与血清游离脂肪酸水平呈负相关，但不与总PDH活性呈负相关。这些和其他的发现指出了PDH相互转化对丙酮酸代谢调节的可能作用。本报告中讨论的观察结果可以解释糖尿病和其他代谢条件下脂肪酸优先氧化的丙酮酸氧化的众所周知的抑制作用。
Pyruvate dehydrogenase (PDH) activity was measured in homogenates from rat heart and kidney. The activity before addition of Mg2+to homogenate was used as a measure of the active form (PDHa) originally present. The activity after incubation in presence of Mg2+is then representative for the total PDH activity present in the tissue. This assay is justified if it is assumed that Mg2+stimulates PDH phosphatase which catalyzes conversion of the inactive (PDHb) to the active form of PDH. Marked changes in the amount of PDHawithout significant changes in total PDH activity were observed in heart and kidney from rats subjected to a variety of metabolic conditions and treatments: on fasting PDHalevels decreased to less than 15% of total activity. On refeeding glucose or fructose PDHalevels rose to normal (70% of total activity). Similarly PDHalevels fell to less than 15% of total activity in heart and kidney of alloxan diabetic rats on withdrawal of insulin and were likewise restored to normal on insulin treatment. Treatment of fasted rats with nicotinic acid—an antilipolytic agent—brought back to normal the PDHalevels lowered by fasting. PDHaactivity but not total PDH activity was inversely related to serum free fatty acid levels. These and other findings point to a possible role of the PDH interconversion for the regulation of pyruvate metabolism. The observations discussed in this report could explain the well known inhibition of pyruvate oxidation in diabetes and in other metabolic conditions where fatty acids are preferentially oxidized.