MECHANISM OF DECARBOXYLATION OF 1,3-DIMETHYLOROTIC ACID - MODEL FOR OROTIDINE 5'-PHOSPHATE DECARBOXYLASE
MECHANISM OF DECARBOXYLATION OF 1,3-DIMETHYLOROTIC ACID - MODEL FOR OROTIDINE 5'-PHOSPHATE DECARBOXYLASE
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DOI：
10.1021/ja00428a035
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发表时间：
1976-01-01
影响因子：
15
通讯作者：
SIEGEL, B
中科院分区：
文献类型：
--
作者：
BEAK, P;SIEGEL, B
1,3-二甲基乙酸在180-220度的磺胺乙烷中通过不同的ph决定途径进行脱羧。C.虽然1,3-二甲基乙酸的电离过程是过量碱存在时的主要途径，但脱羧是由中性溶剂中的两性离子形成引发的。通过测量6-羧基-2,4-二甲氧基吡啶和1-甲基-2,4-二甲氧基吡啶-6-羧酸甜菜碱(7)的CO2损失率来估计两性离子途径的平衡和速率常数。用kcat对orotidine 5”-磷酸脱羧酶7脱羧的速率常数进行比较表明，如果酶提供一个取代平衡的位点，有利于两性离子形式的orotidylic酸，则可以令人满意地解释生物催化。与底物相比，抑制剂6-氮脲单磷酸对酶具有更大的亲和力，为两性离子损失CO2形成的中间体提供了部分模型。
The decarboxylation of 1,3-dimethylorotic acid proceeds by separate pH-determined pathways in sulfolane at 180-220.degree. C. Although a process involving ionization of 1,3-dimethylorotic acid is the major pathway in the presence of excess base, decarboxylation is initiated by zwitterion formation in the neutral solvent. Measurements of the rate of loss of CO2 from 6-carboxy-2,4-dimethoxypyrimidine and 1-methyl-2,4-dimethoxypyrimidinium-6-carboxylate betaine (7) are used to estimate the equilibrium and rate constants for the zwitterionic pathway. Comparison of the rate constant for decarboxylation of 7 with kcat for orotidine 5''-phosphate decarboxylase shows that the biological catalysis can be satisfactorily accounted for if the enzyme provides a site which displaces the equilibrium in favor of the zwitterionic form of orotidylic acid. The inhibitor 6-azauridine monophosphate, which has a greater affinity for the enzyme than does the substrate, provides a partial model for the intermediate formed on loss of CO2 from the zwitterion.