Angiotensin I-converting enzyme-inhibitory peptides from bovine collagen: insights into inhibitory mechanism and transepithelial transport

Yu Fu; Jette Feveile Young; Martin Krøyer Rasmussen; Trine Kastrup Dalsgaard; René Lametsch; Rotimi E Aluko; Margrethe Therkildsen

doi:10.1016/j.foodres.2016.08.037

Angiotensin I-converting enzyme-inhibitory peptides from bovine collagen: insights into inhibitory mechanism and transepithelial transport

Food Res Int. 2016 Nov;89(Pt 1):373-381. doi: 10.1016/j.foodres.2016.08.037. Epub 2016 Aug 28.

Authors

Yu Fu¹, Jette Feveile Young¹, Martin Krøyer Rasmussen¹, Trine Kastrup Dalsgaard¹, René Lametsch², Rotimi E Aluko³, Margrethe Therkildsen⁴

Affiliations

¹ Department of Food Science, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark.
² Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark.
³ Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
⁴ Department of Food Science, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark. Electronic address: margrethe.therkildsen@food.au.dk.

PMID: 28460927
DOI: 10.1016/j.foodres.2016.08.037

Abstract

The inhibitory mechanism and transepithelial transport of angiotensin I-converting enzyme (ACE)-inhibitory peptides (VGPV and GPRGF) derived from Alcalase®- and papain-hydrolyzed bovine collagen were investigated. The inhibitory mechanism of VGPV and GPRGF was experimentally determined to be non-competitive and the results were supported by molecular docking data. In silico and in vitro gastrointestinal digestion indicated that VGPV remained resistant to digestive enzymes, while GPRGF was degraded into smaller ACE-inhibitory peptides (GPR and GF). VGPV and GPRGF were transported across monolayers of human intestinal epithelial Caco-2 cells through paracellular pathway and retained their ACE-inhibitory activities. The present study suggests that VGPV and GPRGF may possibly be absorbed and exert antihypertensive effects in vivo.

Keywords: Collagen peptides; angiotensin I-converting enzyme; digestive enzymes; molecular docking; non-competitive inhibition; transepithelial transport.