FEATURES OF INFLUENCE OF HYPERHOMOCYSTEINEMIA ON THE METABOLISM OF SULFUR-CONTAINING AMINO ACIDS IN THE LIVER OF RATS WITH VARIOUS FUNCTIONS OF THYROID GLAND

  • V. M. Nechiporuk M. Pyrohov Vinnytsia National Medical University
  • N. V. Zaichko M. Pyrohov Vinnytsia National Medical University
  • A. V. Melnik M. Pyrohov Vinnytsia National Medical University
  • E. B. Strutyska M. Pyrohov Vinnytsia National Medical University
  • M. M. Korda I. Horbachevsky Ternopil State Medical University
Keywords: thyroid hormones, sulfur-containing amino acids, remethylation cycle, transsulfuration pathway, homocysteine, cysteine, hydrogen sulfide

Abstract

Introduction. Homocysteine ​​(Hcy) is a sulfur-containing amino acid that is formed during normal acid biosynthesis of amino acids methionine and cysteine. It is known that thyroid hormones have a significant effect on the function of the cardiovascular system. Patients with thyroid pathologies have a high risk of formation cardiovascular diseases. The level of Hcy in patients with hypothyroidism is higher than in patients with hyperthyroidism. 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.

The aim of the study to evaluate in the experiment the effect of hyper- and hypothyroidism at hyperhomocysteinemia on remethylation and transulphation of sulfur-containing amino acids in the liver, HCy, cysteine ​​and H2S levels in the serum blood of experimental rats.

Research Methods. The study was performed on white male rats, which were simulated hyperhomocysteinemia (HHcy), hyper- and hypothyroidism, HHcy with different functions of the thyroid gland. The activity of S-adenosylmethionine synthetase (MAT), S-adenosylhomocysteine hydrolase (S-AHH), betaine-homocysteine methyltransferase (BHMT), cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and cysteine transaminase (CGT), γ-glutamylcysteine ligase (GCL), cysteine dioxygenase (CDO), sulfite oxidase (SO) was determined in the liver. Content of HCy, cysteine, H2S was determined in the serum.

Results and Discussion. HHCy leads to inhibition of the activity of enzymes utilizing Hcy in the liver (BHMT, MAT, S-AHH), cysteine oxidation (CDO, GCL, SO) and H2S synthesis (desulfurase activity of CBS, CSE), which led to a significant increase in serum blood levels of Hcy, cysteine ​​and a decrease in the content of H2S. Hyperthyroidism leads to an increase in the activity of most enzymes of the remethylation cycle (BHMT, S-AMS, S-AHH), transsulfuration pathway (CBS, CGL), increased oxidation of cysteine ​​(CDO, GCL, ІO) and led to a decrease in the level of CG and cysteine, growth level of H2S in the blood. Parallel administration of L-thyroxine to animals with HHCy led to a decrease in the activity of enzymes of the remethylation cycle (BHMT, S-AMS, S-AHH), transsulfuration (CDO, GCL, SO) and desulfuration (CBS, CSE), at the same time there was a positive trend in reducing Hcy, cysteine ​​and an increase in the level of H2S 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 HCy and cysteine ​​and a decrease in the level of H2S. Parallel administration of mercazolile to animals with HHcy led to an increase in the concentration of Hcy in the serum, is a consequence of impaired methylation cycle reactions (S-AMS, S-AHH, BHMT) and transsulfuration (CBS, CGL, CAT) in animals with experimental HHcy.

Conclusions. A high concentrations of HCy and cysteine, a decreasing level of H2S 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.

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Dombkowski, R.A., Russell, M.J., & Olson, К.R. (2004). Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout. Am. J. Physiol. Regul. Integr. Comp. Physiol, 286 (4), 678-685.

Orlowski, M., & Mrister, A. (1971). Partial reaction by γ-glutamylcysteine synthetase and evidence for an activated glutamate intermediate. J. Biol. Chem., 246 (23), 7095-7105.

Gaitonde, M.K. (1967) A spectrophotometric method for direct determination of cysteine in the presence of other naturally occuring amino acid. Biochem. J., 104 (2), 627-633.

Cohen, H.J., & Fridovich, I. (1971). Hepatic sulfite oxidase. Purification and properties. J. Biol. Chem, 246 (2), 359-366.

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Published
2019-04-17
How to Cite
Nechiporuk, V., Zaichko, N., Melnik, A., Strutyska, E., & Korda, M. (2019). FEATURES OF INFLUENCE OF HYPERHOMOCYSTEINEMIA ON THE METABOLISM OF SULFUR-CONTAINING AMINO ACIDS IN THE LIVER OF RATS WITH VARIOUS FUNCTIONS OF THYROID GLAND. Medical and Clinical Chemistry, (1), 103-112. https://doi.org/10.11603/mcch.2410-681X.2019.v0.i1.10028
Section
ORIGINAL INVESTIGATIONS