Urinary excretion of homocysteine-thiolactone in humans.
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 approximately 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.
Chwatko
Grazyna
G
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark 07103, USA.
Jakubowski
Hieronim
H
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005453:Fluorescence; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine*; D006801:Humans; D008875:Middle Aged; D010949:Plasma
D006710:Homocysteine; C007957:homocysteine thiolactone