Effect of thyroid hormones on the sulfur-containing amino acids remethylation and transsulfuration pathways in rat organs
DOI:
https://doi.org/10.11603/mcch.2410-681X.2017.v0.i1.7689Keywords:
thyroid hormones, sulfur-containing amino acids, remethylation cycle, transsulfuration pathway, mocysteine, cysteine, hydrogen sulfide.Abstract
Introduction. Sulfur-containing amino acids affect the vital processes of cells and methylation processes support the redox potential and integrity of cellular systems, incapacitate toxicants and free radicals. Disorders of sulfur-containing amino acids metabolism is associated with different pathologies, including Alzheimer's disease, malignant tumors, neural tube defects, kidneys diseases. The increase of sulfur-containing amino acid homocysteine in the blood is a serious risk factor of cardiovascular diseases such as atherosclerosis, hypertension, venous thrombosis. Regulation of sulfur-containing amino acids metabolism is carried out at different levels, including thyroid hormones. It was shown that hypothyroidism is an independent factor leading to an increase in the concentration of homocysteine in the blood and the risk of cardiovascular diseases development. However, specific molecular mechanisms of the effect of thyroid hormones on sulfur-containing amino acids metabolism are still unknown.
The aim of the study – to investigate experimentally the effect of thyroid hormones on remethylation and transsulfuration pathways in the liver and kidneys, homocysteine, cysteine and hidrogen sulfide contents in the blood serum of experimental animals.
Methods of the research. L-thyroxine and Mercazolil were used for the modeling of hyper- and hypothyroidism, which were confirmed by the content of free thyroxine, free triiod othyronine, thyroid-stimulating hormone in serum.
Results and Discussion. In the liver and kidneys of animals with hypothyroidism a decrease in the activity of remethylation cycle enzymes (S-adenosylmethionine synthetase, S-adenosylhomocysteine hydrolase and betaine-homocysteine methyltransferase), as well as transsulfuration pathway enzymes (cystathionine β-synthase, cystathionine γ-lyase, cysteine transaminase) was observed. At the same time, introduction of L-thyroxine increased the activity of these enzymes in the liver and kidney tissues. Hyperthyroidism caused the decrease of homocysteine concentration whereas hypothyroidism increased the levels of homocysteine, cysteine and decreased the hydrogen sulpide content in blood.
Conclusions. Disorders of remethylation and transsulfuration of sulfur-containing amino acids in organs might be important risk factors of atherosclerosis, endothelial dysfunction, and hypercoagulation development.
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