Effects of diabetes on oxidative decarboxylation of branched-chain keto acids.
Effects of diabetes on oxidative decarboxylation of branched-chain keto acids.
复制标题
糖尿病对支链酮酸氧化脱羧的影响。
DOI：
10.1152/ajpendo.1980.239.3.e215
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
Buse,MG
中科院分区：
文献类型：
--
作者：
May,ME;Mancusi,VJ;Aftring,RP;Buse,MG
氧化脱羧基是亮氨酸降解的第一个不可逆步骤。以[1-14C]α-酮基异己酸为底物，在无细胞大鼠肝脏标本中研究了链脲佐菌素糖尿病对这一反应的影响。糖尿病组大鼠肝组织支链酮酸脱氢酶(BCKD)活性(每克肝脏或每毫克蛋白)增加，但BCKD活性与其他线粒体标志物的比值不变。糖尿病患者胞浆中不需要NAD、CoA或NADP的支链酮酸脱羧酶活性(匀浆活性的15%-22%)也增加。糖尿病患者的胰岛素治疗使所有组分的酶活性恢复正常。BCKD在匀浆中的表观Km为43-45微米；糖尿病使表观Vmax从165nmoxmin-1xg组织-1增加到260nmolxmin-1xg-1。相比之下，对照组细胞内α-酮基异己酸脱羧基的Km为270微米，糖尿病导致Km较低(210微米)和Vmax较高。肾上腺切除对对照组的匀浆活性没有影响，但部分逆转了糖尿病相关的增加。对照组的胰升糖素预处理不影响活性。综上所述，肝脏中不同的线粒体和胞浆酶脱羧基α-酮基异己酸。糖尿病大鼠肝脏降解亮氨酸碳骨架的能力增强主要归因于线粒体质量的相对增加。
Oxidative decarboxylation is the first irreversible step in the degradation of leucine. The effect of streptozotocin diabetes on this reaction was studied in cell-free rat liver preparations, using [1-14C]alpha-ketoisocaproate as substrate. Diabetes increased the branched-chain ketoacid dehydrogenase (BCKD) activity (per g liver or per mg protein) of homogenates, but the ratios of homogenate BCKD activity to other mitochondrial markers remained unchanged. A cytosolic branched-chain ketoacid decarboxylase activity (15-22% of homogenate activity), which did not require NAD, CoA, or NADP, was also increased in diabetics. Insulin treatment of diabetics normalized enzyme activity in all fractions. The apparent Km of BCKD in homogenates was 43-45 microM; diabetes increased the apparent Vmax from 165 nmol x min-1 x g tissue-1 to 260 nmol x min-1 x g-1. In contrast, the Km for cytosolic alpha-ketoisocaproate decarboxylation was 270 microM in controls, and diabetes resulted in both a lower Km (210 microM) and a higher Vmax. Adrenalectomy did not affect activity in homogenates from controls, but partially reversed the diabetes-associated increase. Glucagon pretreatment of controls did not affect activity. In summary, distinct mitochondrial and cytosolic enzymes decarboxylate alpha-ketoisocaproate in liver. The increased hepatic capacity of diabetic rats to degrade the carbon skeleton of leucine is attributed mainly to a relative increase in mitochondrial mass.