Hunter Gregory A, Rivera Edwin, Ferreira Gloria C
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Arch Biochem Biophys. 2005 May 15;437(2):128-37. doi: 10.1016/j.abb.2005.03.007. Epub 2005 Mar 22.
5-aminolevulinic acid (ALA) is the committed biological precursor to porphyrins. At supraphysiological concentrations ALA can dimerize to form 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY), which transfers electrons to XTT in a reaction that does not require metal ions and is specifically inhibited by superoxide dismutase. The formation of DHPY from ALA follows dimerization kinetics with a pK of 7.8+/-0.1. At pH 11.2, DHPY is relatively stable, but when the pH is dropped to 6.0 rapid conversion to 2,5-(beta-carboxyethyl)pyrazine occurs via an intermediate with an absorption maximum of 370 nm. Formation of this intermediate is pH-dependent with a pK of 6.0+/-0.1. These data indicate that ALA dimerizes to produce superoxide from a protonated form of DHPY. The significance of these results with respect to the concentrations of ALA used in photodynamic therapy, and the increased incidence of liver cancer in acute intermittent porphyria, is discussed.
5-氨基乙酰丙酸（ALA）是卟啉的特定生物前体。在超生理浓度下，ALA可二聚形成3,6-二氢吡嗪-2,5-二丙酸（DHPY），后者在一个不需要金属离子且受超氧化物歧化酶特异性抑制的反应中将电子转移给XTT。从ALA形成DHPY遵循二聚动力学，其pK为7.8±0.1。在pH 11.2时，DHPY相对稳定，但当pH降至6.0时，它会通过一个最大吸收波长为370 nm的中间体快速转化为2,5-（β-羧乙基）吡嗪。该中间体的形成取决于pH，其pK为6.0±0.1。这些数据表明，ALA二聚可从DHPY的质子化形式产生超氧化物。本文讨论了这些结果对于光动力疗法中使用的ALA浓度以及急性间歇性卟啉症中肝癌发病率增加的意义。
