支链2-氧代酸对发育中大鼠和人脑中2-氧代戊二酸脱氢酶复合体的抑制作用。
Inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in developing rat and human brain.
作者信息
Patel M S
出版信息
Biochem J. 1974 Oct;144(1):91-7. doi: 10.1042/bj1440091.
Abstract
- The effect of the branched-chain amino acids, namely leucine, isoleucine and valine and their corresponding 2-oxo acids on the metabolism of 2-oxoglutarate by developing rat and human brain preparations was investigated. 2. The decarboxylation of 2-oxo[1-(14)C]glutarate to (14)CO(2) by mitochondria from adult rat brain was inhibited by the branched-chain 2-oxo acids whereas the branched-chain amino acids had no inhibitory effect on this process. 3. The activity of 2-oxoglutarate dehydrogenase complex was about 0.2unit/g of brain from 2-day-old rats and increased by about fourfold reaching an adult value by the end of the third postnatal week. 4. The K(m) value for 2-oxoglutarate of the 2-oxoglutarate dehydrogenase complex in rat and human brain was 100 and 83mum respectively. 5. The branched-chain 2-oxo acids competitively inhibited this enzyme from suckling and adult rats brains as well as from foetal and adult human brains, whereas the branched-chain amino acids had no effect on this enzyme. 6. Approximate K(i) values for the branched-chain 2-oxo acids found for this enzyme were in the range found for these 2-oxo acids in plasma from patients with maple-syrup-urine disease. 7. The possible significance of the inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in brains of untreated patients with maple-syrup-urine disease is discussed in relation to the energy metabolism and the biosynthesis of lipids from ketone bodies.
摘要
- 研究了支链氨基酸（即亮氨酸、异亮氨酸和缬氨酸）及其相应的2-氧代酸对发育中的大鼠和人脑组织中2-氧代戊二酸代谢的影响。2. 成年大鼠脑线粒体将2-氧代[1-(14)C]戊二酸脱羧生成(14)CO(2)的过程受到支链2-氧代酸的抑制，而支链氨基酸对该过程无抑制作用。3. 2-氧代戊二酸脱氢酶复合物的活性在2日龄大鼠脑中约为0.2单位/克脑，到出生后第三周结束时增加约四倍，达到成年值。4. 大鼠和人脑组织中2-氧代戊二酸脱氢酶复合物对2-氧代戊二酸的K(m)值分别为100和83μM。5. 支链2-氧代酸竞争性抑制乳鼠和成年大鼠脑以及胎儿和成年人类脑组织中的这种酶，而支链氨基酸对该酶无影响。6. 该酶对支链2-氧代酸的近似K(i)值在枫糖尿症患者血浆中这些2-氧代酸的范围内。7. 讨论了支链2-氧代酸对未经治疗的枫糖尿症患者脑中2-氧代戊二酸脱氢酶复合物的抑制作用在能量代谢和酮体脂质生物合成方面的可能意义。
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