Martins Peçanha Flavia Letícia, Dos Santos Reinaldo Sousa, da-Silva Wagner Seixas
Instituto de Bioquímica Médica Leopoldo de MeisLaboratório de Adaptações Metabólicas, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Bioquímica Médica Leopoldo de MeisLaboratório de Adaptações Metabólicas, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Rio de Janeiro, Brazil
Endocr Connect. 2017 Jul;6(5):311-322. doi: 10.1530/EC-17-0059. Epub 2017 May 8.
The thyroid hormones (THs), triiodothyronine (T) and thyroxine (T), are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK) is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T, 0.25 µg/g, i.p. during 21 days) mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, = 10), gastrocnemius (369.2% ± 112.4, = 10) and heart (142.2% ± 13.6, = 10) muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T administration (single dose of T, 1.25 µg/g, i.p.) did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.
甲状腺激素（THs），即三碘甲状腺原氨酸（T₃）和甲状腺素（T₄），在机体代谢中非常重要，并调节葡萄糖的利用。己糖激酶（HK）负责糖酵解的第一步，催化葡萄糖转化为6-磷酸葡萄糖。已在不同的细胞区室中发现了HK，并且该酶具有新的功能。研究了甲状腺功能亢进对小鼠组织亚细胞葡萄糖磷酸化的影响。取出组织，从正常甲状腺和甲状腺功能亢进（T₃，0.25μg/g，腹腔注射21天）小鼠中分离亚细胞组分，并测定HK活性。与对照组相比，甲状腺功能亢进组比目鱼肌（312.4%±67.1，n = 10）、腓肠肌（369.2%±112.4，n = 10）和心肌（142.2%±13.6，n = 10）颗粒部分的葡萄糖磷酸化增加。HK活性在脑或肝脏中不受影响。在所研究的所有组织的可溶性部分中，未观察到HK活性有相关变化。急性给予T₃（单剂量T₃，1.25μg/g，腹腔注射）未调节HK活性。有趣的是，HK mRNA水平保持不变，而T₃处理使与线粒体结合的HK增加，提示存在转录后机制。AKT途径分析显示，与正常甲状腺组相比，甲状腺功能亢进组腓肠肌中AKT和GSK3B磷酸化增加了2.5倍。综上所述，我们首次表明THs特异性地调节颗粒部分的HK活性，并且这种作用似乎受AKT和GSK3B途径的控制。
