Montero-Lomelí M, Galvão D, Morais B B, Nardi A E
Programa de Biologia Molecular e Biotecnologia, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brasil.
Braz J Med Biol Res. 2007 Jan;40(1):19-25. doi: 10.1590/s0100-879x2007000100003.
Lithium has been used for the last five decades to treat bipolar disorder, but the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293 cells, it is inhibited by lithium in the therapeutic concentration range. We measured the phosphoglucomutase activity in erythrocytes and the inhibitor constant for lithium in a population of healthy subjects and compared them to those of bipolar patients treated with lithium or carbamazepine. The specific activity of phosphoglucomutase measured in vitro in erythrocytes from control subjects presented a normal distribution, with the difference between the lowest and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min-1). Comparison of phosphoglucomutase activity in untreated bipolar patients and control subjects showed no significant difference, whereas comparison between bipolar patients treated with carbamazepine or lithium revealed significantly lower mean values in patients treated with carbamazepine (747.3 +/- 27.6 vs 879.5 +/- 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of lithium needed to inhibit phosphoglucomutase activity by 50%, a bimodal distribution among the population tested was obtained. The concentration of LiCl needed to inhibit phosphoglucomutase activity by 50% was 0.35 to 1.8 mM in one group of subjects and in the other it was 3 to 4 mM. These results suggest that phosphoglucomutase activity may be significant in patients with bipolar disorder treated with lithium and carbamazepine.
在过去的五十年里，锂一直被用于治疗双相情感障碍，但其治疗效果的分子基础尚不清楚。磷酸葡萄糖变位酶是糖原代谢中的关键酶。在酵母、兔和人胚肾293细胞中，它在治疗浓度范围内会受到锂的抑制。我们测量了健康受试者群体中红细胞内磷酸葡萄糖变位酶的活性以及锂的抑制常数，并将其与接受锂或卡马西平治疗的双相情感障碍患者的相应指标进行了比较。在对照组受试者红细胞中体外测量的磷酸葡萄糖变位酶的比活性呈正态分布，最低活性与最高活性之间的差异约为2倍（0.53 - 1.10 nmol mg Hb-1 min-1）。未经治疗的双相情感障碍患者与对照组受试者的磷酸葡萄糖变位酶活性比较无显著差异，而接受卡马西平或锂治疗的双相情感障碍患者之间的比较显示，接受卡马西平治疗的患者平均活性值显著更低（分别为747.3 ± 27.六岁 vs 879.5 ± 35.9 pmol mg Hb-1 min-1）。当我们研究抑制磷酸葡萄糖变位酶活性50%所需的锂浓度时，在测试人群中获得了双峰分布。在一组受试者中，抑制磷酸葡萄糖变位酶活性50%所需的LiCl浓度为0.35至1.8 mM，而在另一组中为3至4 mM。这些结果表明，磷酸葡萄糖变位酶活性在接受锂和卡马西平治疗的双相情感障碍患者中可能具有重要意义。
