P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi‐ target activity, since it inhibits both 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type‐9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5‐frag) and LPKHSDAD (P5‐ met), and that both P5 and P5‐met are linearly absorbed by differentiated human intestinal Caco‐2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5‐met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi‐target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.

Trans-Epithelial Transport, Metabolism and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met) / C. Lammi, G. Aiello, C. Bollati, J. Li, M. Bartolomei, G. Ranaldi, S. Ferruzza, E.M.A. Fassi, G. Grazioso, Y. Sambuy, A. Arnoldi. - In: NUTRIENTS. - ISSN 2072-6643. - 13:3(2021 Mar 05). [10.3390/nu13030863]

Trans-Epithelial Transport, Metabolism and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met)

C. Lammi
Primo
;
C. Bollati;J. Li;M. Bartolomei;E.M.A. Fassi;G. Grazioso;A. Arnoldi
Ultimo
2021

Abstract

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi‐ target activity, since it inhibits both 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type‐9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5‐frag) and LPKHSDAD (P5‐ met), and that both P5 and P5‐met are linearly absorbed by differentiated human intestinal Caco‐2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5‐met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi‐target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.
Caco‐2 cells; food bioactive peptides; LDLR; PCSK9; trans‐epithelial transport;
Settore CHIM/10 - Chimica degli Alimenti
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/823616
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