Effects of milk casein-derived tripeptides Ile-Pro-Pro, Val-Pro-Pro, and Leu-Pro-Pro on enzymes processing vasoactive precursors in vitro

Abstract

Milk-based drinks containing casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown topossess antihypertensive and vascularendothelium-protecting properties in hy-pertensive animal models. Furthermorein clinical intervention trials they reduceblood pressure and arterial stiffness. Theexact mechanisms are not known, but inhibition of angiotensin converting enzyme 1 (ACE1) has been suggested mainlyto mediate these beneficial effects

The present study investigated the in vitro effects of three tripeptides: Ile-Pro-Pro, Val-Pro-Pro and leucine-proline-proline (Leu-Pro-Pro) on four reninangiotensin system enzymes: ACE1ACE2, chymase, and cathepsin G. Also their effects on arginase I, a critical enzyme in L-arginine-nitric oxide pathway were studied

It was shown, apparently for the firsttime, that the inhibitory effects of Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro on ACE1 at micromolar concentrations arecompetitive in nature. Therefore the efficacy of inhibition is largely dependent onthe amount of substrate present. Inhibition of ACE2 and arginase I was reachedonly at concentrations three orders of magnitude greater. No inhibition of chymase and cathepsin G was observed by the tripeptides

The findings support the hypothesis that Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro act favourably on blood pressure mainly by selective inhibition of ACE1.

Key words

Angiotensin-converting enzyme - Arginas - Ile-Pro-Pro - Leu-Pro-Pro - Selective inhibition - Val-Pro-Pro

• Literatur

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