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Articles in PresS, published online ahead of print December 10, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00403.2002
Submitted on September 9, 2002
Accepted on December 6, 2002
1 Department of Internal Medicine, Nephrology Division, University of Genoa, Genoa, Italy
* To whom correspondence should be addressed. E-mail: gari{at}unige.it.
Homocysteine (Hcy), a putative risk factor of cardiovascular diseases, as well as other aminothiols (Cysteine and Cysteinyl-Glycine) increase in blood with aging and chronic diseases. However, both sites and mechanisms responsible for the maintenance of circulating pools of aminothiols in humans are currently poorly understood. In the present study we used the organ balance technique across the kidney, splanchnic organs, and the lower limb in subjects undergoing diagnostic central venous catheterizations in order to get insight into the renal and extrarenal exchange of aminothiols in humans. While Hcy was only released in low amounts from the leg tissues (-0.31±0.10 µmol|min;p<0.05), Cysteinyl-Glycine (Cys-Gly) (a peptide derived from GSH hydrolysis) was released both by the leg (-1.1±0.20 µmol|min) and splanchnic organs (-0.76±0.04 µmol/min),whereas Cys was released by the kidney and taken up by splanchnic organs. The kidney removed ~90% of the Cys-Gly released into the circulation. The removal of Cys-Gly by the kidney depended on Cys-Gly arterial levels (r=0.78; p<0.02) and showed a high fractional extraction (~26%), with clearance rates which were slightly higher than GFR. Although the average kidney removal of Hcy was not statistical significant, the fractional extraction of Hcy across the kidney varied directly with renal plasma flow (RPF) (r=0.66;p<0.05). Our data show that thiol metabolism in humans is a compartmentalized, inter-organ process involving fluxes of individual aminothiols which are parallel and of opposite sign among peripheral tissues, splanchnic organs and kidney. Cys-Gly is released by peripheral tissue and splanchnic organs from GSH hydrolysis and is taken up by the kidney by glomerular filtration (GFR); the kidney returns Cys to the circulation to preserve substrate availability for GSH synthesis. On the other hand Hcy is released by peripheral tissues in low amounts and its removal by the kidney seems to depend on blood supply. These findings may help to explain several alterations in aminothiol metabolism which are observed in patients with chronic diseases.
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