Clinical Chemistry
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Clinical Chemistry 51: 408-415, 2005. First published December 2, 2004; 10.1373/clinchem.2004.042531
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(Clinical Chemistry. 2005;51:408-415.)
© 2005 American Association for Clinical Chemistry, Inc.

Endocrinology and Metabolism

Urinary Excretion of Homocysteine-Thiolactone in Humans

Grayna Chwatko1,1 and Hieronim Jakubowski1,2,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, Poznan, 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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