The role of paraoxonase 1 in the detoxification of homocysteine thiolactone.
The thioester homocysteine (Hcy)-thiolactone, product of an error-editing reaction in protein biosynthesis, forms when Hcy is mistakenly selected by methionyl-tRNA synthetase. Accumulating evidence suggests that Hcy-thiolactone plays an important role in atherothrombosis. The thioester chemistry of Hcy-thiolactone underlies its ability to form isopeptide bonds with protein lysine residues, which impairs or alters protein function and has pathophysiological consequences including activation of an autoimmune response and enhanced thrombosis. Mammalian organisms, including human, have evolved the ability to eliminate Hcy-thiolactone. One such mechanism involves paraoxonase 1 (PON1), which has the ability to hydrolyze Hcy-thiolactone. This article outlines Hcy-thiolactone pathobiology and reviews evidence documenting the role of PON1 in minimizing Hcy-thiolactone and N-Hcy-protein accumulation.
Jakubowski
Hieronim
H
Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland. jakubows@umdnj.edu
D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism / Q000502:physiology*; D015551:Autoimmunity; D005340:Fibrinogen / Q000737:chemistry; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007107:Immune System; D008718:Methionine-tRNA Ligase / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D012307:Risk Factors; D013927:Thrombosis / Q000378:metabolism
D006710:Homocysteine; D005340:Fibrinogen; C007957:homocysteine thiolactone; D043303:Aryldialkylphosphatase; D008718:Methionine-tRNA Ligase