Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease

Abstract

Acrolein (2-propenal) is ubiquitously present in (cooked) foods and in the environment. It is formed from carbohydrates, vegetable oils and animal fats, amino acids during heating of foods, and by combustion of petroleum fuels and biodiesel. Chemical reactions responsible for release of acrolein include heat-induced dehydration of glycerol, retro-aldol cleavage of dehydrated carbohydrates, lipid peroxidation of polyunsaturated fatty acids, and Strecker degradation of methionine and threonine. Smoking of tobacco products equals or exceeds the total human exposure to acrolein from all other sources. The main endogenous sources of acrolein are myeloperoxidase-mediated degradation of threonine and amine oxidase-mediated degradation of spermine and spermidine, which may constitute a significant source of acrolein in situations of oxidative stress and inflammation. Acrolein is metabolized by conjugation with glutathione and excreted in the urine as mercapturic acid metabolites. Acrolein forms Michael adducts with ascorbic acid in vitro, but the biological relevance of this reaction is not clear. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis.

Figure 1

Formation of acrolein from glucose via hydroxy acetone (a). RA, retro aldol-cleavage.

Figure 2

Proposed formation of acrolein from arachidonic acid according to Esterbauer and co-workers [5].

Figure 3

Hypothetical formation of acrolein, 1-alken-3-ones, and 1-alken-3-ols from 3-hydroperoxy-1-alkenes (authors’ interpretation of results obtained by Pan and co-workers [22]).

Figure 4

Formation of acrolein from methionine. The first three reaction steps are collectively known as the Strecker degradation of an α-amino acid.

Figure 5

Proposed reaction pathway for the formation of acrolein from threonine mediated by myeloperoxidase (MPO) (adapted from Anderson et al. [7]).

Figure 6

Amine oxidase-mediated catabolism of spermine yields acrolein and 3-aminopropanal.

Figure 7

Metabolism of acrolein.

Figure 8

Michael addition of ascorbate to acrolein: ,ascorbylation of acrolein’. DMF, dimethylformamide.

Figure 9

Adduction of deoxyguanosine to acrolein.

Figure 10

Adduction of acrolein to amino acid residues in proteins.

Figure 11

MALDI-MS/MS spectrum of the HICAT-labeled acrolein-modified peptide from ADP/ATP translocase 1 (ADT1_RAT, a.a. 245-258) found in heart mitochondria from 24-month-old untreated rats. As precursor ion for the MS/MS experiment, the peptide ion with m/z 2116.0 was used. The fragment ion data indicate that Cys-256 was modified by acrolein and the resulting protein carbonyl was subsequently tagged by the aldehyde/keto-specific probe HICAT (adapted from [137]).