Gender characteristics of hyperhomocysteinemia effect on metabolism of sulfur-containing amino acids and hydrogen sulfide in liver
DOI:
https://doi.org/10.11603/mcch.2410-681X.2017.v0.i1.7352Keywords:
homocysteine, cysteine, hydrogen sulfide, blood, liver enzymes.Abstract
Introduction. Sulfur amino acid disorders are recognized as metabolic risk factors for cardiovascular pathology. However, the question of the involvement of sulfur amino acids in the formation of the gender-defined pathology of cardiovascular system remains unclear.
The aim of the study – research the impact of thiolactone hyperhomocysteinemia (HHC) on blood levels of sulfur-containing metabolites and enzymes activity in metabolism of homocysteine, cysteine and hydrogen sulfide in the liver of rats of both sexes.
Methods of the research. Experiments were conducted on 40 white laboratory rats of both sexes weighing 220–280 g. Hyperhomocysteinemia was modeled by long-term intragastric administration of thiolactone D,L-homocysteine, dosage 100 mg / kg, in 1 % starch solution once per day for 28 days. The research determines the content of homocysteine, cysteine and hydrogen sulfide in blood serum and activity of enzymes in the liver – cystathionine-γ-lyase, cystathionine-β-synthase, cysteine aminotransferase, methionine adenosyltransferase, cysteine dioxygenase and γ-glutamylcysteine ligase.
Results and Discussion. Hyperhomocysteinemia initiates gender-defined changes in the content of sulfur-containing metabolites in the serum of rats: increase homocysteine and cysteine and reduction of hydrogen sulfide is 111; 59.2 and 59.4 % in males (females – 82.4, 38.0 and 47.5 %, p<0.05) respectively compared to the control group.
HHC in males has led to a more distinct decreased in liver enzyme activity of homocysteine methylation and transsulfuration (on 20.5–24.8 % in males and on 13.4–15.4 % in females, p <0.05), enzymes of cysteine degradation in oxidative and conjugation ways (in 21.1–22.0 % in males and on 13.4–15.3 % in females, p<0.05) and H2S-synthesizing enzymes (20.6–25.9 % in males and on 13.5–17.5 % in females, p<0.05) compared to the control group.
Conclusions. It was shown, thiolactone homocysteine administration is accompanied by the rise of homocysteine, cysteine and the reduced levels of hydrogen sulfide in blood in individuals of both sexes, but more significant changes were observed in males. In addition, gender defined changes in the metabolism of sulfur-containing compounds in the liver were registered: male rats showed significantly greater decrease in liver enzyme activity of homocysteine remethylation and transsulfuration, cysteine degradation enzymes and synthesis of hydrogen sulfide in the liver compared to female rats.
References
1. Moat, S.J. (2008). Plasma total homocysteine: instigator or indicator of cardiovascular disease? Ann. Clin. Biochem., 45, 345-348.
Wang, R. (2010). Hydrogen sulfide: the third gasotransmitter in biology and medicine. Antioxid. Redox. Signal., 12 (9), 1061-1064.
Barna, O.M. (2007). Henderna kardiolohiia. Proektsiia na arytmii u zhinok [Gender cardiology. Projection on arrhythmias in women]. Meditsinskie aspekty zdorovia Zhenshchiny – Medical Aspects of Women's Health, 4 (7), 14-18 [in Ukrainian].
Regitz-Zagrosek, V., Oertelt-Prigione, S., & Seeland U. (2010). Sex and gender differences in myocardial hypertrophy and heart failure. Circ. J. 74 (7), 1265-1273.
Stangl, G.I., Weisse, K., & Dinger, C. (2007). Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats. Exp. Biol. Med. (Maywood) 232 (1), 81-87.
Melnyk, A.V. & Pentiuk, O.O. (2009). Aktyvnist enzymiv syntezu hidrohen sulfidu v nyrkakh shchuriv [Аctivity of hydrogen sulfide production enzymes in kidneys of rats]. Ukr. biokhim. zhurnal – Ukrainian Biochemical Journal, 81 (4), 12-22. [in Ukrainian].
Goldstein, J.L., Campbell, B.K., Gartler, S.M. (1972). Cystathionine synthase activity in human lymphocytes: induction by phytohemagglutinin. J. Clin. Invest, 51 (4), 1034-1037.
Chiang, P.K., & Cantoni G.L. (1977). Activation of methionine for transmethylation. Purification of the S-adenosylmethionine synthetase of bakers' yeast and its separation into two forms. J. Biol. Chem., 252 (13), 4506-4513.
Stipanuk, M.H., De la Rosa J., & Hirschberger, L.L. (1990). Catabolism of cyst(e)ine by rat renal cortical tubules. J. Nutr., 120 (5), 450-458.
Orlowski, M., & Mrister A. (1971). Partial reaction by г-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.
Zaichko, N.V., Pentiuk, N.O., Pentiuk, L.O., Melnyk, A.V., & Andrushko, I.I. (2009). Vyznachennia vmistu hidrohen sulfidu v syrovattsi krovi [Determination of hydrogen sulfide in blood serum]. Visnyk naukovykh doslidzhen – Bulletin of Scientific Research, 1 (59), 29-32 [in Ukrainian].
Kopeck, J. Krijt, J., & Rakov K. (2011). Restoring assembly and activity of cystathionine в-synthase mutants by ligands and chemical chaperones. J. Inherit. Metab. Dis. 34 (1), 39-48.
Avila, M.A., Corrales, F.J., & Ruiz F. (1998). Specific interaction of methionine adenosyltransferase with free radicals. Biofactors, 8 (1-2), 27-32.
Driggers, C.M., Kean, K.M., & Hirschberger L.L. (2016). Structure-Based Insights into the Role of the Cys-Tyr Crosslink and Inhibitor Recognition by Mammalian Cysteine Dioxygenase. J. Mol. Biol., 428 (20), 3999-4012.
Fukagawa, N.K., Martin, J.M., & Wurthmann A. Sex-related differences in methionine metabolism and plasma homocysteine concentrations. Am. J. Clin. Nutr., 72 (1), 22-29.
