2-氧代酸对大鼠脑内丙酮酸利用及脂肪酸合成的不同影响
Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain.
作者信息
Clark J B, Land J M
出版信息
Biochem J. 1974 Apr;140(1):25-9. doi: 10.1042/bj1400025.
Abstract
- The effects of 2-oxo-4-methylpentanoate, 2-oxo-3-methylbutanoate and 2-oxo-3-methylpentanoate on the activity of pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase, (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old rats were investigated. 2. The pyruvate dehydrogenase enzyme activity was competitively inhibited by 2-oxo-3-methylbutanoate with respect to pyruvate with a K(i) of 2.04mm but was unaffected by 2-oxo-4-methylpentanoate or 2-oxo-3-methylpentanoate. 3. The citrate synthase activity was inhibited competitively (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)
7.2mm) and 2-oxo-3-methylbutanoate (K(i)14.9mm) but not by 2-oxo-3-methylpentanoate. 4. The acetyl-CoA carboxylase activity was not inhibited significantly by any of the 2-oxo acids investigated. 5. The fatty acid synthetase activity was competitively inhibited (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)930mum) and 2-oxo-3-methylpentanoate (K(i)3.45mm) but not by 2-oxo-3-methylbutanoate. 6. Preliminary experiments indicate that 2-oxo-4-methylpentanoate and 2-oxo-3-phenylpropionate (phenylpyruvate) significantly inhibit the ability of intact brain mitochondria from 14-day-old rats to oxidize pyruvate. 7. The results are discussed with reference to phenylketonuria and maple-syrup-urine disease. A biochemical mechanism is proposed to explain the characteristics of these diseases.
摘要
研究了2-氧代-4-甲基戊酸酯、2-氧代-3-甲基丁酸酯和2-氧代-3-甲基戊酸酯对14日龄大鼠脑内丙酮酸脱氢酶（EC 1.2.4.1）、柠檬酸合酶（EC 4.1.3.7）、乙酰辅酶A羧化酶（EC 6.4.1.2）和脂肪酸合成酶活性的影响。
2-氧代-3-甲基丁酸酯对丙酮酸脱氢酶活性相对于丙酮酸具有竞争性抑制作用，K(i)为2.04mmol，但不受2-氧代-4-甲基戊酸酯或2-氧代-3-甲基戊酸酯影响。
柠檬酸合酶活性受到2-氧代-4-甲基戊酸酯（K(i)约为7.2mmol）和2-氧代-3-甲基丁酸酯（K(i)约为14.9mmol）的竞争性抑制（相对于乙酰辅酶A），但不受2-氧代-3-甲基戊酸酯抑制。
所研究的任何一种2-氧代酸均未对乙酰辅酶A羧化酶活性产生显著抑制。
脂肪酸合成酶活性受到2-氧代-4-甲基戊酸酯（K(i)约为930μmol）和2-氧代-3-甲基戊酸酯（K(i)约为3.45mmol）的竞争性抑制（相对于乙酰辅酶A），但不受2-氧代-3-甲基丁酸酯抑制。
初步实验表明，2-氧代-4-甲基戊酸酯和2-氧代-3-苯基丙酸酯（苯丙酮酸）显著抑制14日龄大鼠完整脑线粒体氧化丙酮酸的能力。
结合苯丙酮尿症和枫糖尿症对结果进行了讨论。提出了一种生化机制来解释这些疾病的特征。
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