甲基柠檬酸的生物合成。
The biosynthesis of methylcitrate.
作者信息
Weidman S W, Drysdale G R
出版信息
Biochem J. 1979 Jan 1;177(1):169-74. doi: 10.1042/bj1770169.
Abstract
Citrate synthase catalyses the formation in vitro of two diastereoisomers of methylcitrate from propionyl-CoA and oxaloacetate. The proportion of diastereoisomers produced is temperature-sensitive. In the presence of oxaloacetate and a thiol trap, the enzyme catalyses the exchange of both alpha-protons of propionyl-CoA with 2H2O. The pro-S-proton at the alpha-carbon atom is exchanged 15 times faster with 2H2O than is the pro-R-proton. The exchanges are over 1000 and 100 times faster respectively than Vmax. These results are interpreted in the light of recent reports that 2R,3S- and 2S,3S-methylcitrates are produced by the enzyme-catalysed condensation and also excreted by patients with propionic acidaemia.
摘要
柠檬酸合酶在体外催化由丙酰辅酶A和草酰乙酸形成柠檬酸甲酯的两种非对映异构体。所产生的非对映异构体的比例对温度敏感。在草酰乙酸和硫醇捕获剂存在的情况下，该酶催化丙酰辅酶A的两个α-质子与2H2O进行交换。α-碳原子上的前-S-质子与2H2O的交换速度比前-R-质子快15倍。这些交换分别比Vmax快1000倍和100倍以上。根据最近的报道，2R,3S-和2S,3S-甲基柠檬酸是由酶催化缩合产生的，并且丙酸血症患者也会排出这些物质，对这些结果进行了解释。
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本文引用的文献
1
SUCCINIC THIOKINASE. I. PURIFICATION OF THE ENZYME FROM PIG HEART.琥珀酰硫激酶。一、从猪心纯化该酶。
J Biol Chem. 1964 Jun;239:1961-7.
2
THE ABSOLUTE STEREOCHEMICAL COURSE OF CITRIC ACID BIOSYNTHESIS.柠檬酸生物合成的绝对立体化学过程。
Proc Natl Acad Sci U S A. 1963 Nov;50(5):981-8. doi: 10.1073/pnas.50.5.981.
3
Studies of the mechanism of action of the condensing enzyme.缩合酶作用机制的研究。
J Biol Chem. 1959 May;234(5):999-1003.
4
The effect of univalent cations on activities catalyzed by bovine-liver propionyl-CoA carboxylase.单价阳离子对牛肝丙酰辅酶A羧化酶催化活性的影响。
Biochim Biophys Acta. 1967 Jul 11;139(2):487-501. doi: 10.1016/0005-2744(67)90052-6.
5
6
[On the biochemical function of biotin. IX. The steric course in the carboxylation of propionyl-CoA].[关于生物素的生化功能。IX. 丙酰辅酶A羧化作用的立体化学过程]
Biochem Z. 1965 Aug 6;342(3):256-71.
7
The enzymatic carboxylation of propionyl coenzyme A. Studies involving deuterated and tritiated substrates.
J Biol Chem. 1968 Apr 10;243(7):1551-7.
8
Stereochemistry of the interconversions of citrate and acetate catalyzed by citrate synthase, adenosine triphosphate citrate lyase, and citrate lyase.
Biochemistry. 1971 Jun 8;10(12):2267-72. doi: 10.1021/bi00788a013.
9
Isolation and identification of methylcitrate, a major metabolic product of propionate in patients with propionic acidemia.丙酸血症患者中丙酸主要代谢产物柠檬酸甲酯的分离与鉴定。
J Biol Chem. 1972 Apr 10;247(7):2200-4.
10
Controls of citrate synthase activity.
Life Sci. 1974 Nov 15;15(10):1695-710. doi: 10.1016/0024-3205(74)90172-6.
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