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Urinary Excretion of Homocysteine-Thiolactone in Humans

Grayna Chwatko^1,1 and Hieronim Jakubowski^1,2,a

¹ Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ.
² Institute of Bioorganic Chemistry, Polish Academy of Sciences, Pozna, Poland.

^aAddress correspondence to this author at: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07103. Fax 973-972-8982; e-mail jakubows{at}umdnj.edu.

Background: A metabolite of homocysteine (Hcy), the thioester Hcy-thiolactone, has been implicated in coronary heart disease in humans. Because inadvertent reactions of Hcy-thiolactone with proteins can lead to cell and tissue damage, the ability to detoxify or eliminate Hcy-thiolactone is essential for biological integrity. We examined the hypothesis that the human body eliminates Hcy-thiolactone by urinary excretion.

Methods: We used a sensitive HPLC method with postcolumn derivatization and fluorescence detection to examine Hcy-thiolactone concentrations in human urine and plasma.

Results: We discovered a previously unknown pool of Hcy-thiolactone in human urine. Urinary concentrations of Hcy-thiolactone (11–485 nmol/L; n = 19) were 100-fold higher than those in plasma (<0.1–22.6 nmol/L; n = 20). Urinary Hcy-thiolactone accounted for 2.5–28.3% of urinary total Hcy, whereas plasma Hcy-thiolactone accounted for <0.002–0.29% of plasma total Hcy. Urinary concentrations of Hcy-thiolactone, but not of total Hcy, were negatively correlated with urinary pH. Clearance of Hcy-thiolactone, relative to creatinine, was 0.21–6.96. In contrast, relative clearance of Hcy was 0.001–0.003.

Conclusions: The analytical methods described here can be used to quantify Hcy-thiolactone in biological fluids. Using these methods we showed that the human body eliminates Hcy-thiolactone by urinary excretion. Our data also suggest that the protonation status of its amino group affects Hcy-thiolactone excretion.

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