title: Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides.
abstract: Xanthine oxidase (XO) and dipeptidyl peptidase IV (DPP-IV) inhibition by amino acids and dipeptides was studied. Trp and Trp-containing dipeptides (Arg-Trp, Trp-Val, Val-Trp, Lys-Trp and Ile-Trp) inhibited XO. Three amino acids (Met, Leu and Trp) and eight dipeptides (Phe-Leu, Trp-Val, His-Leu, Glu-Lys, Ala-Leu, Val-Ala, Ser-Leu and Gly-Leu) inhibited DPP-IV. Trp and Trp-Val were multifunctional inhibitors of XO and DPP-IV. Lineweaver and Burk analysis showed that Trp was a non-competitive inhibitor of XO and a competitive inhibitor of DPP-IV. Molecular docking with Autodock Vina was used to better understand the interaction of the peptides with the active site of the enzyme. Because of the non-competitive inhibition observed, docking of Trp-Val to the secondary binding sites of XO and DPP-IV is required. Trp-Val was predicted to be intestinally neutral (between 25% and 75% peptide remaining after 60 min simulated intestinal digestion). These results are of significance for the reduction of reactive oxygen species (ROS) and the increase of the half-life of incretins by food-derived peptides.
authors.affiliation: Department of Life Sciences and Food for Health Ireland (FHI), University of Limerick, Castletroy, Limerick, Ireland.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Nongonierma
authors.forename: Catherine
authors.initials: C
authors.lastname: Mooney
authors.forename: Denis C
authors.initials: DC
authors.lastname: Shields
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D004151:Dipeptides / Q000737:chemistry*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry*; D007700:Kinetics; D007930:Leucine / Q000737:chemistry*; D008715:Methionine / Q000737:chemistry*; D062105:Molecular Docking Simulation; D013552:Swine; D014357:Trypsin / Q000737:chemistry*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D008715:Methionine; D014969:Xanthine Oxidase; D018819:Dipeptidyl Peptidase 4; D014357:Trypsin; D007930:Leucine