l-Cysteine enhances nutrient absorption via a cystathionine-β-synthase-derived H2S pathway in rodent jejunum

Summary Hydrogen sulphide (H 2 S) is generated endogenously from l -cysteine ( l -Cys) by the enzymes cystathionine- β -synthase (CBS) and cystathionine- γ -lyase (CSE). In addition, l -Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether l -Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo l -Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of l -Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as l -Cys) an inhibitor of CBS. Measurements of the short-circuit current ( I sc ) in the rat jejunum epithelium revealed that l -Cys (1 mmol/L; 6 min before the administration of l -alanine) enhances Na + -coupled l -alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of l -Cys), but not d , l -propargylglycine (PAG;1 mmol/L; 10 min before the administration of l -Cys), a CSE inhibitor. Notably, l -Cys-evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of l -Cys), a K + channel blocker. Together, the data indicate that l -Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition.