title: Short communication: Inhibition of angiotensin 1-converting enzyme by peptides derived from variants of bovine β-casein upon apical exposure to a Caco-2 cell monolayer.
abstract: This study investigated the consequence of genetically contingent amino acid substitutions in bovine β-casein (CN) genetic variants A1, A2, B, and I on the structure and bioactive potential of peptides following in vitro digestion. The β-CN variants were digested in vitro using pepsin and pancreatin, and a peptide profile was obtained by liquid chromatography tandem mass spectrometry, revealing among others, the β-casomorphin precursor peptides VYPFPGPIHN and VYPFPGPIPN, derived from variant A1/B and from A2/I, respectively. These 2 peptides were synthesized and assessed for angiotensin 1-converting enzyme (ACE) inhibitory capacity before and after incubation with a monolayer of Caco-2 intestinal cells. The VYPFPGPIHN was a stronger ACE inhibitor than VYPFPGPIPN, with the concentration needed to reach half-maximal inhibition (IC50) of 123 ± 14.2 μM versus 656 ± 7.6 μM. Exposure to a Caco-2 intestinal cell monolayer did not affect ACE inhibition by VYPFPGPIHN, but resulted in an almost 2-fold increase in inhibition by VYPFPGPIPN after incubation. Subsequent tandem mass spectrometric analysis identified the truncated peptide VYPFPGPIP, suggesting hydrolysis by a cell membrane associated peptidase. Thus, genetic variation in bovine β-CN results in the generation of peptides that differ in bioactivity, and are differently affected by intestinal brush border peptidases.
authors.affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Petrat-Melin
authors.affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.
authors.forename: Thao T
authors.initials: TT
authors.lastname: Le
authors.affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.
authors.forename: Hanne S
authors.initials: HS
authors.lastname: Møller
authors.affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark.
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Larsen
authors.affiliation: Department of Food Science, Aarhus University, 8830 Tjele, Denmark. Electronic address: jettef.young@food.au.dk.
authors.forename: Jette F
authors.initials: JF
authors.lastname: Young
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D018938:Caco-2 Cells; D002364:Caseins / Q000737:chemistry*; D002417:Cattle; D006801:Humans; D010455:Peptides / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002364:Caseins; D010455:Peptides; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin 1-converting enzyme; beta-casein; bioactive peptide; genetic variant; in vitro digestion