Interorgan exchange of aminothiols in humans.

Abstract

In the present study, we used organ balance across the kidney, splanchnic organs, and lower limb in subjects undergoing diagnostic central venous catheterizations to gain insight into the renal and extrarenal exchange of aminothiols in humans. Although Hcy was released only in low amounts from leg tissues, Cys-Gly (a peptide derived from GSH hydrolysis) was released by both the leg and splanchnic organs, whereas Cys was released by the kidney and taken up by splanchnic organs. The kidney removed approximately 90% of the Cys-Gly released into the circulation. Removal of Cys-Gly by the kidney depended on Cys-Gly arterial levels and showed a high fractional extraction ( approximately 26%), with clearance rates slightly higher than the glomerular filtration rate (GFR). Although the average kidney removal of Hcy was not statistically significant, the fractional extraction of Hcy across the kidney varied directly with renal plasma flow. Our data show that thiol metabolism in humans is a compartmentalized interorgan process involving fluxes of individual aminothiols that 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 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 explain several alterations in aminothiol metabolism observed in patients with chronic diseases.