Tonin Anelise Miotti, Ferreira Gustavo Costa, Schuck Patrícia Fernanda, Viegas Carolina Maso, Zanatta Angela, Leipnitz Guilhian, Seminotti Bianca, Duvall Wannmacher Clóvis Milton, Wajner Moacir
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, RS, Brasil.
Metab Brain Dis. 2009 Jun;24(2):349-60. doi: 10.1007/s11011-009-9131-z. Epub 2009 Apr 16.
Accumulation of lysine (Lys) in tissues and biochemical fluids is the biochemical hallmark of patients affected by familial hyperlysinemia (FH) and also by other inherited neurometabolic disorders. In the present study, we investigated the in vitro effect of Lys on various parameters of energy metabolism in cerebral cortex of 30-day-old Wistar rats. We verified that total (tCK) and cytosolic creatine kinase activities were significantly inhibited by Lys, in contrast to the mitochondrial isoform which was not affected by this amino acid. Furthermore, the inhibitory effect of Lys on tCK activity was totally prevented by reduced glutathione, suggesting a possible role of reactive species oxidizing critical thiol groups of the enzyme. In contrast, Lys did not affect (14)CO(2) production from [U-(14)C] glucose (aerobic glycolytic pathway) and [1-(14)C] acetic acid (citric acid cycle activity) neither the various activities of the electron transfer chain and synaptic Na(+)K(+)-ATPase at concentrations as high as 5.0 mM. Considering the importance of creatine kinase (CK) activity for brain energy metabolism homeostasis and especially ATP transfer and buffering, our results suggest that inhibition of this enzyme by Lys may contribute to the neurological signs presented by symptomatic patients affected by FH and other neurodegenerative disorders in which Lys accumulates.
赖氨酸（Lys）在组织和生物化学体液中的蓄积是受家族性高赖氨酸血症（FH）以及其他遗传性神经代谢疾病影响的患者的生化标志。在本研究中，我们研究了赖氨酸对30日龄Wistar大鼠大脑皮质能量代谢的各种参数的体外作用。我们证实，赖氨酸可显著抑制总肌酸激酶（tCK）和胞质肌酸激酶的活性，而线粒体同工型不受该氨基酸的影响。此外，还原型谷胱甘肽可完全阻止赖氨酸对tCK活性的抑制作用，提示活性物质可能氧化了该酶关键的巯基。相反，赖氨酸在高达5.0 mM的浓度下，对[U-(14)C]葡萄糖（有氧糖酵解途径）和[1-(14)C]乙酸（柠檬酸循环活性）产生的(14)CO(2)没有影响，对电子传递链和突触Na(+)K(+)-ATP酶的各种活性也没有影响。考虑到肌酸激酶（CK）活性对脑能量代谢稳态尤其是ATP转移和缓冲的重要性，我们的结果表明，赖氨酸对该酶的抑制作用可能导致FH和其他赖氨酸蓄积导致的神经退行性疾病的有症状患者出现神经学症状。
