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.丙酰辅酶A的酶促羧化作用。涉及氘代和氚代底物的研究。
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.柠檬酸合酶、三磷酸腺苷柠檬酸裂解酶和柠檬酸裂解酶催化的柠檬酸与乙酸相互转化的立体化学
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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