Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, Ctra Valldemosa km 7.5, E-07122 Palma de Mallorca, Spain.
J Phys Chem A. 2012 Mar 1;116(8):1897-905. doi: 10.1021/jp2116033. Epub 2012 Feb 14.
Pyridoxal 5'-phosphate (PLP) is a B(6) vitamer acting as an enzyme cofactor in various reactions of aminoacid metabolism and inhibiting glycation of biomolecules. Nonenzymatic glycation of aminophospholipids alters the stability of lipid bilayers and cell function as a result. Similarly to protein glycation, aminophospholipid glycation initially involves the formation of a Schiff base. In this work, we studied the formation of Schiff bases between PLP and two compounds mimicking the polar head of natural aminophospholipids, namely: O-phosphorylethanolamine and O-phospho-D,L-serine. Based on the results, the pH-dependence of the microscopic constants of the two PLP-aminophosphate systems studied is identical with that for PLP-aminoacid systems. However, the rate and equilibrium formation constants for the Schiff bases of the aminophosphates are low relative to those for the aminoacids. A theoretical study by density functional theory of the formation mechanism for the Schiff bases of PLP with the two aminophospholipid analogues confirmed that the activation energy of formation of the Schiff bases is greater with aminophosphates; on the other hand, that of hydrolysis is essentially similar with aminoacids and aminophosphates.
吡哆醛 5'-磷酸（PLP）是 B（6）维生素的一种变体，作为各种氨基酸代谢反应的酶辅因子，并抑制生物分子的糖化。非酶糖化的氨基磷脂会改变脂质双层的稳定性和细胞功能。与蛋白质糖化类似，氨基磷脂糖化最初涉及到希夫碱的形成。在这项工作中，我们研究了 PLP 与两种模拟天然氨基磷脂极性头的化合物之间形成希夫碱的过程，即：O-磷酸乙醇胺和 O-磷酸-D,L-丝氨酸。基于结果，所研究的两种 PLP-氨基磷酸系统的微观常数的 pH 依赖性与 PLP-氨基酸系统的 pH 依赖性相同。然而，氨基磷酸的希夫碱的速率和平衡形成常数相对于氨基酸的要低。通过密度泛函理论对 PLP 与两种氨基磷脂类似物形成希夫碱的机制进行的理论研究证实，希夫碱形成的活化能随着氨基磷酸的增加而增大；另一方面，水解的活化能与氨基酸和氨基磷酸基本相似。
