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J Agric Food Chem. 2018 Aug 22;66(33):8737-8743. doi: 10.1021/acs.jafc.8b03648. Epub 2018 Aug 13.

Characterization of Angiotensin-Converting Enzyme Inhibitory Activity of X-Hyp-Gly-Type Tripeptides: Importance of Collagen-Specific Prolyl Hydroxylation.

Author information

1
Nippi Research Institute of Biomatrix , 520-11 Kuwabara , Toride , Ibaraki 302-0017 , Japan.
2
Faculty of Agriculture , Kyushu University , 6-10-1 Hakozaki, Higashi-ku , Fukuoka 812-8581 , Japan.
3
Department of Pharmacognosy, Faculty of Pharmacy , Mansoura University , Mansoura 35516 , Egypt.

Abstract

Hydroxyproline (Hyp) is a collagen-specific amino acid formed by post-translational hydroxylation of Pro residues. Various Hyp-containing oligopeptides are transported into the blood at high concentrations after oral ingestion of collagen hydrolysate. Here we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of X-Hyp-Gly-type tripeptides. In an in vitro assay, ginger-degraded collagen hydrolysate enriched with X-Hyp-Gly-type tripeptides dose-dependently inhibited ACE and various synthetic X-Hyp-Gly-type tripeptides showed ACE-inhibitory activity. In particular, strong inhibition was observed for Leu-Hyp-Gly, Ile-Hyp-Gly, and Val-Hyp-Gly with IC50 values of 5.5, 9.4, and 12.8 μM, respectively. Surprisingly, substitution of Hyp with Pro dramatically decreased inhibitory activity of X-Hyp-Gly, indicating that Hyp is important for ACE inhibition. This finding was supported by molecular docking experiments using Leu-Hyp-Gly/Leu-Pro-Gly. We further demonstrated that prolyl hydroxylation significantly enhanced resistance to enzymatic degradation by incubation with mouse plasma. The strong ACE-inhibitory activity and high stability of X-Hyp-Gly-type tripeptides highlight their potential for hypertension control.

KEYWORDS:

X-Hyp-Gly; angiotensin-converting enzyme; collagen hydrolysate; ginger; hydroxyproline

PMID:
30060651
DOI:
10.1021/acs.jafc.8b03648
[Indexed for MEDLINE]

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