TY - JOUR AU - Nechiporuk, V. M. AU - Zaichko, N. V. AU - Melnik, A. V. AU - Strutyska, E. B. AU - Korda, M. M. PY - 2019/04/17 Y2 - 2024/03/28 TI - FEATURES OF INFLUENCE OF HYPERHOMOCYSTEINEMIA ON THE METABOLISM OF SULFUR-CONTAINING AMINO ACIDS IN THE LIVER OF RATS WITH VARIOUS FUNCTIONS OF THYROID GLAND JF - Medical and Clinical Chemistry JA - MCCh VL - 0 IS - 1 SE - ORIGINAL INVESTIGATIONS DO - 10.11603/mcch.2410-681X.2019.v0.i1.10028 UR - https://ojs.tdmu.edu.ua/index.php/MCC/article/view/10028 SP - 103-112 AB - <p><strong><em>Introduction</em></strong><strong><em>.</em></strong><em> Homocysteine ​​(</em><em>Hcy</em><em>) is a sulfur-containing amino acid that is formed during normal acid biosynthesis of amino</em><em> acids</em><em> methionine and cysteine. It is known that thyroid hormones have a significant effect on the function of the cardiovascular system. </em><em>P</em><em>atients with thyroid pathologies</em><em> have a</em> <em>h</em><em>igh risk of </em><em>formation</em><em> cardiovascular diseases. </em><em>T</em><em>he level of </em><em>Hcy</em><em> in patients with hypothyroidism is higher than in patients with hyperthyroidism. </em><em>At the same time, it is unclear whether the development of cardiovascular diseases in patients with thyroid gland pathology is associated with changes in the content of Hcy in blood. </em></p><p><strong><em>The aim of the study</em></strong><em> –</em><em> to evaluate in the experiment the effect of hyper- and hypothyroidism </em><em>at</em><em> hyperhomocysteinemia on remethylation and transulphation of sulfur-containing amino acids in the liver, </em><em>HCy</em><em>, cysteine ​​and H<sub>2</sub>S levels in the serum blood of experimental </em><em>rats</em><em>.</em></p><p><strong><em>Research </em></strong><strong><em>M</em></strong><strong><em>ethods.</em></strong><em> The study was performed on white male rats, which </em><em>were </em><em>simulated </em><em>h</em><em>yperhomocysteinemia (HHcy), hyper- and hypothyroidism, HHcy with different functions of the thyroid gland. The activity </em><em>of </em><em>S-adenosylmethionine synthetase (</em><em>MAT</em><em>), </em><em>S-adenosylhomocysteine hydrolase (</em><em>S-AHH</em><em>)</em><em>, betaine-homocysteine methyltransferase</em><em> (BHMT)</em><em>, cystathionine-β-synthase</em><em> (CBS)</em><em>, cystathionine-γ-lyase</em><em> (CSE)</em><em> and cysteine transaminase</em><em> (CGT)</em><em>, γ-glutamylcysteine ligase (GCL), cysteine dioxygenase (CDO), sulfite oxidase (</em><em>SO</em><em>)</em><em> was determined in the liver</em><em>. </em><em>C</em><em>ontent of </em><em>HCy</em><em>, cysteine, H<sub>2</sub>S</em><em> was determined in the serum</em><em>.</em></p><p><strong><em>Results and </em></strong><strong><em>D</em></strong><strong><em>iscussion.</em></strong> <em>HHCy</em><em> leads to inhibition of the activity of enzymes utilizing Hc</em><em>y</em><em> in the liver (</em><em>BHMT</em><em>, MAT, </em><em>S-AHH</em><em>), cysteine </em><em>oxidation</em><em> (CDO, GCL, </em><em>S</em><em>O) and H<sub>2</sub>S synthesis (desulfurase activity of CBS, </em><em>CSE</em><em>), which led to a significant increase in serum blood levels of </em><em>Hcy</em><em>, cysteine ​​and a decrease in the content of H<sub>2</sub>S. Hyperthyroidism leads to an increase in the activity of most enzymes of the remethylation cycle (BHMT, S-AMS, S-A</em><em>H</em><em>H), </em><em>transsulfuration</em><em> pathway</em><em> (CBS, CGL), increased oxidation of cysteine ​​(CDO, GCL, ІO) and led to a decrease in the level of CG and cysteine, growth </em><em>level</em><em> of H<sub>2</sub>S in the blood. Parallel administration of L-thyroxine to animals with </em><em>HHCy</em><em> led to a decrease in the activity of enzymes of the remethylation cycle (</em><em>BHMT</em><em>, S-AMS, S-A</em><em>H</em><em>H), transsulfuration (CDO, GCL, </em><em>S</em><em>O) and </em><em>desulfuration</em><em> (CBS, </em><em>CSE</em><em>), at the same time there was a positive trend in reducing </em><em>Hcy</em><em>, cysteine ​​and an increase in the level of H<sub>2</sub>S in the blood. Hypothyroidism led to a decrease in the liver activity of the enzyme cycle remethylation (BHMT, S-AMS, S-AGH) and transsulfuration processes (CBS, CGL, CAT), an increase in the content of </em><em>HCy</em><em> and cysteine ​​and a decrease in the level of H<sub>2</sub>S. Parallel administration of mercazol</em><em>ile</em><em> to animals with </em><em>HHcy</em><em> led to an increase in the concentration of </em><em>Hcy</em><em> in the serum, is a consequence of impaired methylation cycle reactions (S-AMS, S-A</em><em>H</em><em>H, BHMT) and transsulfuration (CBS, CGL, CAT) in animals with experimental </em><em>HHcy</em><em>.</em></p><p><strong><em>Conclusions.</em></strong><em> A high concentrations of HCy and cysteine, a decreasing level of H<sub>2</sub>S in hypothyroidism can be significant risk factors for the development of atherosclerosis, oxidative stress, endothelial dysfunction and hypercoagulation in diseases accompanied by low levels of thyroid hormones. Our findings are a prerequisite for further experimental studies, which will improve the understanding of the mechanisms of formation of pathological conditions associated with impaired metabolism of sulfur-containing amino acids in HHcy with different thyroid function, and optimize approaches for pharmacotherapy.</em></p> ER -