Nechiporuk V, Zaichko N, Korda М, Melnyk A, Koloshko O
Vinnytsia National Pirogov Memorial Medical University; I. Horbachevsky Ternopil State Medical University, Ukraine.
Georgian Med News. 2017 Oct(271):96-102.
Hyper- and hypothyroidism are some of the most common endocrinopathies that cause many metabolic disorders including amino acids metabolism. However, a specific molecular mechanism of thyroid hormones influence on sulphur-containing amino acids metabolism has not been established. The aim of our research was to investigate experimentally the influence of thyroid gland functional state on the main enzymatic systems of sulphur-containing amino acids metabolism in liver and kidneys, the content of homocysteine, cysteine and H2S in blood. The rats were administered with L-thyroxine and mercazolil to simulate the states of hyper- and hypothyroidism, which were confirmed by the content of fT3, fT4 and TSH in the blood. In liver and kidneys of the animals with hypothyroidism we observed the decrease in the activity of enzymes of remethylation cycle of S-adenosylmethioninsyntase, S-adenosylhomocysteinhyhdrolase, betaine-homocysteine methyltransferase. Suppression of transsulfuration transformation of homocysteine to cysteine in hypothyroidism was mainly due to the inhibition of cystathionine synthase activity of cystathionine-β-synthase, wherein cystathionase activity of cystathionine-γ-lyase was not changed. In animals with hypothyroidism we also noticed the inhibition of cysteine desulfunation reactions: the activity of enzymes of cystathionine-β-synthase, cystathionine-γ-lyase and cysteine aminotransferase significantly decreased in liver and kidneys. Experimental hyperthyroidism was accompanied by increase in activity of remethylation cycle enzymes, increase in cystationine synthase activity of cystathionine-β-synthase in liver and activity of these enzymes in kidneys. The simulation of hyperthyroidism led to the decrease of homocysteine concentration, and of hypothyroidism - to the increase of homocysteine and cysteine concentrations and reduced H2S content in blood of the animals. Thus, the significant risk factors for the development of atherosclerosis, endothelial dysfunction and hypercoagulation in hypothyroid conditions may be the disorders in the processes of remethylation, transsulfuration, and desulfuration of sulphur-containing amino acids in organs.
甲状腺功能亢进和减退是一些最常见的内分泌疾病，可导致包括氨基酸代谢在内的许多代谢紊乱。然而，甲状腺激素对含硫氨基酸代谢影响的具体分子机制尚未明确。我们研究的目的是通过实验研究甲状腺功能状态对肝脏和肾脏中含硫氨基酸代谢的主要酶系统以及血液中同型半胱氨酸、半胱氨酸和硫化氢含量的影响。给大鼠施用L-甲状腺素和甲巯咪唑以模拟甲状腺功能亢进和减退状态，这通过血液中游离三碘甲状腺原氨酸（fT3）、游离甲状腺素（fT4）和促甲状腺激素（TSH）的含量得以证实。在甲状腺功能减退动物的肝脏和肾脏中，我们观察到S-腺苷甲硫氨酸合成酶、S-腺苷同型半胱氨酸水解酶、甜菜碱-同型半胱氨酸甲基转移酶的再甲基化循环酶活性降低。甲状腺功能减退时同型半胱氨酸向半胱氨酸的转硫转化受到抑制，主要是由于胱硫醚-β-合酶的胱硫醚合成酶活性受到抑制，而胱硫醚-γ-裂解酶的胱硫醚酶活性未发生变化。在甲状腺功能减退的动物中，我们还注意到半胱氨酸脱硫反应受到抑制：肝脏和肾脏中胱硫醚-β-合酶、胱硫醚-γ-裂解酶和半胱氨酸转氨酶的活性显著降低。实验性甲状腺功能亢进伴随着再甲基化循环酶活性增加、肝脏中胱硫醚-β-合酶的胱硫醚合成酶活性增加以及肾脏中这些酶的活性增加。甲状腺功能亢进的模拟导致同型半胱氨酸浓度降低，而甲状腺功能减退则导致动物血液中同型半胱氨酸和半胱氨酸浓度增加以及硫化氢含量降低。因此，甲状腺功能减退状态下动脉粥样硬化、内皮功能障碍和高凝状态发展的重要危险因素可能是器官中含硫氨基酸再甲基化、转硫和脱硫过程的紊乱。
