Juknat A A, Kotler M L, Batlle A M
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995 May;111(1):143-50. doi: 10.1016/0742-8413(94)00085-8.
The response of nerve cells to high exogenous aminolevulinic acid (ALA) concentrations was studied by examining the changes in its uptake and in porphyrin biosynthesis. ALA was shown to be taken up by cerebral cortex particles by a non-saturable process. As opposed to other previously described experimental systems, it was also observed that 84-87% of porphyrins formed was found within the cells. Exposure of cerebral cortex particles to high exogenous ALA (0.8-4.0 mM) showed that ALA can be accumulated in relatively high concentrations in brain cells (21.04 +/- 1.05 nmol/mg protein). Under these experimental conditions, porphyrin biosynthesis was found to be markedly inhibited (52%). 2.4 mM ALA caused an initial stimulation of glucose uptake after 1 hr incubation and a later fall to below control values, being consistent with the fact that acute porphyric crisis could be precipitated by the action of ALA on energy metabolism. ALA toxicity could be due both to its accumulation in the cells and to deficient heme concentrations, with an additional effect on glucose metabolism. These findings provide the basis for a useful brain tissue model to investigate the nature of the metabolic mechanisms occurring in acute intermittent porphyria (AIP) patients.
通过检测神经细胞对外源高浓度δ-氨基-γ-酮戊酸（ALA）的摄取变化以及卟啉生物合成的变化，研究了神经细胞对其的反应。结果表明，ALA通过一种非饱和过程被大脑皮质颗粒摄取。与之前描述的其他实验系统不同的是，还观察到所形成的卟啉中有84 - 87%存在于细胞内。将大脑皮质颗粒暴露于外源高浓度ALA（0.8 - 4.0 mM）中，结果显示ALA能够以相对较高的浓度在脑细胞中蓄积（21.04 +/- 1.05 nmol/mg蛋白质）。在这些实验条件下，发现卟啉生物合成受到显著抑制（52%）。2.4 mM的ALA在孵育1小时后引起葡萄糖摄取的初始刺激，随后降至对照值以下，这与ALA作用于能量代谢可引发急性卟啉症危机这一事实相符。ALA的毒性可能既归因于其在细胞内的蓄积，也归因于血红素浓度不足，此外还对葡萄糖代谢有影响。这些发现为研究急性间歇性卟啉症（AIP）患者体内发生的代谢机制的本质提供了一个有用的脑组织模型。
