Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin.

Christina Engels,Kristopher Mcneill,Christophe Lacroix,Jianbo Zhang,Corinne Bieri,Shana J Sturla,Marc-Olivier Ebert,Marc J A Stevens,Clarissa Schwab

doi:10.1038/srep36246

Abstract

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

Highlights

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin
We integrated data from ion-exclusion chromatography with pulsed-amperometric detection (IC-PAD), NMR and ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode (MRM UPLC-ESI-MS/MS) to gain information regarding all compounds of the reuterin system namely 3-HPA, its hydrate 1,1,3-propanetriol, its dimer 2-(2-hydroxyethyl)-4-hydroxy-1,3-dioxane and acrolein
Already a hundred years ago, Voisenet discovered the formation of acrolein when a Bacillus species was grown in the presence of glycerol and it was hypothesized that glycerol was first dehydrated to 3-HPA before acrolein was formed in a secondary reaction[31,32]

Summary

Introduction

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. In aqueous solution 3-HPA exists in an equilibrium with mainly its hydrate 1,1,3-propanetriol and its dimer 2-(2-hydroxyethyl)−4-hydroxy-1,3-dioxane[16]; other multimeric forms have been reported[17,18] This dynamic system has been called reuterin after Lactobacillus reuteri, the best studied model organism for 3-HPA production (Fig. 1). In addition to its well-investigated antimicrobial functions, reuterin is implicated in the conjugation of heterocyclic amines (HCAs), a process of potential relevance to the bioavailability of toxicants in the human gut[24,25]. Because HCAs are mutagenic and possible human carcinogens contributing to the increased risk of colorectal cancer from eating meat, a detailed understanding of their physiological transformation pathways is a critical component of risk analysis[27,28,29,30]

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