TREATMENT OF RATS WITH GLUCAGON OR MANNOHEPTULOSE INCREASES MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE ACTIVITY AND DECREASES SUCCINYL-COA CONTENT IN LIVER
TREATMENT OF RATS WITH GLUCAGON OR MANNOHEPTULOSE INCREASES MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE ACTIVITY AND DECREASES SUCCINYL-COA CONTENT IN LIVER
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DOI：
10.1042/bj2620159
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发表时间：
1989-08-15
影响因子：
4.1
通讯作者：
BRAND, MD
中科院分区：
文献类型：
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作者：
QUANT, PA;TUBBS, PK;BRAND, MD
在以各种方式处理以增加生酮通量的动物中，快速冷冻大鼠肝脏提取物中3-羟基-3-甲基戊二酰-CoA（HMG-CoA）合酶（EC 4.1.3.5）的活性加倍。2.约90%的活性测量是线粒体和线粒体活性的变化占主导地位的总酶活性的变化。3.升高的HMG-CoA合酶活性在整个肝线粒体分离过程中持续存在。4.线粒体内琥珀酰辅酶A含量较低，在全肝匀浆和线粒体分离的动物与胰高血糖素或单庚酮糖。5. HMG-CoA合酶活性从牛和大鼠肝脏线粒体内琥珀酰辅酶A水平呈负相关，当这些被人为操纵。在这些条件下，线粒体之间的差异，从控制和糖尿病治疗的大鼠被取消。6.这些发现表明，胰高血糖素可以降低线粒体内琥珀酰辅酶A浓度，这反过来又可以调节线粒体HMG-CoA合酶。他们支持这一假设，从乙酰辅酶A的酮体的形成可能是由线粒体HMG-CoA合酶的琥珀酰化的程度进行调节。
The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (EC 4.1.3.5) in extracts of rapidly frozen rat livers was doubled in animals treated in various ways to increase ketogenic flux. 2. Some 90% of the activity measured was mitochondrial and changes in mitochondrial activity dominated changes in total enzyme activity. 3. The elevated HMG-CoA synthase activities persisted throughout the isolation of liver mitochondria. 4. Intramitochondrial succinyl-CoA content was lower in whole liver homogenates and in mitochondria isolated from animals treated with glucagon or monoheptulose. 5. HMG-CoA synthase activity in mitochondria from both ox and rat liver was negatively correlated with intramitochondrial succinyl-CoA levels when these were manipulated artificially. Under these conditions, the differences between mitochondria from control and hormone-treated rats were abolished. 6. These findings show that glucagon can decrease intramitochondrial succinyl-CoA concentration, and that this in turn can regulate mitochondrial HMG-CoA synthase. They support the hypothesis that the formation of ketone bodies from acetyl-CoA may be regulated by the extent of succinylation of mitochondrial HMG-CoA synthase.