Molecular mechanisms of biotoxicity of homocysteine--facts and hypotheses |
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Authors: | Turski Wojciech Antoni Bald Edward |
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Institution: | Chair of Health and Physical Education, Holy Cross Academy, Branch at Piotrków Trybunalski, 114/118 Slowackiego St., 97-300 Piotrk6w Trybunalski, Poland. |
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Abstract: | In the article, the main pathways of homocysteine metabolism are described, i.e. transsulfuration to cysteine and glutathione, as well as remethylation to methionine. Furthermore, formation of homocysteine thiolactone through editing mechanism with methionyl t-RNA syntethase and unusual reactivity of thiolactone against lysine epsilonNH2 groups of proteins as well as calcium dependent enzymatic hydrolysis of thiolactone are discussed. The effects of oxidative stress related to homocysteine are also reviewed. Finally, possible links of homocysteine to NO and arginine metabolism are discussed, including ADMA (N(G),N(G)-dimethylarginine). The links between metabolism of homocysteine, adenosine and other nucleosides are emphasized. In conclusion, the N-homocysteilation of proteins with thiolactone changing enormously their properties seems to be the main reason of biotoxicity of homocysteine during atherosclerosis and other diseases. |
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