Inhibition of Glutathione and S-Allyl Glutathione on Pancreatic Lipase: Analysis Through in Vitro Kinetics, Fluorescence Spectroscopy and in Silico Docking

Inhibition of pancreatic lipase (PL) is considered one of the important therapeutic interventions against obesity. In the present study, the inhibition of porcine (mammalian) PL (PPL) by two tripeptides glutathione (GSH) and s-allyl glutathione (SAG) was studied. In vitro kinetic analysis was done to determine the inhibition of GSH and SAG against PPL. The binding of GSH and SAG with PPL was elucidated by fluorescence spectroscopy analysis. Docking and molecular dynamics (MD) simulation analysis was carried out to understand the intermolecular interaction between both GSH and SAG with PPL as well as human PL (HPL). Both GSH and SAG inhibited PPL in mixed non-competitive manner. The IC₅₀ value for GSH and SAG against PPL was found to be 2.97 and 6.4 mM, respectively. Both GSH and SAG quenched the intrinsic fluorescence of PPL through static quenching that is through forming complex with the PPL. SAG and GSH interacted with amino acids involved in catalysis of both PPL and HPL. MD simulation showed interactions of SAG and GSH with both PPL and HPL were stable. These results would lead to the further studies and application of GSH and SAG against obesity through inhibition of PL.

Keywords: Fluorescence quenching; Glutathione; Lipase; Peptide inhibitor; S-allyl glutathione.