What is it about?
Elevated levels of homocysteine thiolactone, a toxic metabolite which has the ability to damage proteins, predict heart attacks in humans. An enzyme called paraoxonase 1 (PON1), carried on high-density lipoprotein (HDL) in the blood, exerts protective effects on human cardiovascular system. However, the function of PON1 in the human vasculature is not fully understood. In this report we have shown for the first time that genetic variation in the PON1 gene affects PON1’s ability to detoxify homocysteine thiolactone in humans.
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Why is it important?
These findings are important because they identify PON1/HDL as a determinant of homocysteine thiolactone levels in humans. We have provided evidence that PON1/HDL detoxifies homocysteine thiolactone and that this function is modified by the genetic variation in PON1 activity in humans. Identifying determinants of homocysteine thiolactone levels will help to design strategies to reduce its accumulation.
Perspectives
As a discoverer of PON1's ability to detoxify homocysteine thiolactone back in 2000, it is rewarding to be able to demonstrate that this function is important in the human body. Writing this article was a great pleasure as it has as co-authors my long standing collaborators without whom this article would not be possible.
Hieronim Jakubowski Jakubowski
Rutgers The State University of New Jersey
Read the Original
This page is a summary of: Paraoxonase 1 Q192R genotype and activity affect homocysteine thiolactone levels in humans, The FASEB Journal, May 2018, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201800346r.
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