Callahan Brian P, Wolfenden Richard
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
J Am Chem Soc. 2004 Apr 14;126(14):4514-5. doi: 10.1021/ja031720j.
A covalent imminium adduct, formed by condensation of aminomalonate with acetone, undergoes decarboxylation (k = 0.03 s-1 at 25 degrees C) in water 30 000 times more rapidly than does aminomalonate in the absence of acetone. A Brønsted plot of the observed rates of decarboxylation of these and other ionized carboxylic acids, as a function of the pKC-H values of the carbon acids generated by their decarboxylation, exhibits a betalg value of 0.7, indicating that the structures of the transition states for decarboxylation of the carboxylate forms of these acids approaches the structures of the carbanions generated by their decarboxylation. On the basis of an estimated pKC-H value for benzene in water ( approximately 43), extrapolation of that Brønsted plot leads to the prediction that benzoate decarboxylation should proceed at detectable rates in water at temperatures below the critical point. That prediction was confirmed experimentally. Using this same relationship, and extrapolating to the observed rate constant for enzymatic decarboxylation of orotidine 5'-monophosphate, we estimate that the "effective" pKa value of the 6-CH group of uridine 5'-monophosphate, the product of decarboxylation, is 9.5 at the active site of yeast OMP decarboxylase.
由氨基丙二酸酯与丙酮缩合形成的共价亚胺鎓加合物，在水中发生脱羧反应（25℃时k = 0.03 s-1），其速度比在无丙酮情况下氨基丙二酸酯的脱羧速度快30000倍。以这些及其他离子化羧酸的观测脱羧速率对其脱羧生成的碳酸的pKC-H值作图，得到的布朗斯特图显示βlg值为0.7，这表明这些酸的羧酸盐形式脱羧反应过渡态的结构接近其脱羧生成的碳负离子的结构。根据水中苯的估计pKC-H值（约43），对该布朗斯特图进行外推，预测苯甲酸酯在低于临界点的温度下于水中应能以可检测的速率进行脱羧反应。该预测已通过实验得到证实。利用同样的关系，并外推至乳清苷5'-单磷酸酶促脱羧的观测速率常数，我们估计脱羧产物尿苷5'-单磷酸6-CH基团在酵母OMP脱羧酶活性位点的“有效”pKa值为9.5。
