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.

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

“…Acrolein is a known environmental hazard, as it can be formed by incomplete combustion of organic matter, and occurs at significant levels in wood and tobacco smoke, as well as in processed foods [36]. It can also be formed endogenously by oxidative metabolism of non-lipid precursors such as spermine, spermidine, threonine and methionine, and glycerol [37]. While it is known that acrolein could be formed from overheating of cooking oils, for some years there was debate over whether it represented a significant product of lipid oxidation in vivo.…”

“…While it is known that acrolein could be formed from overheating of cooking oils, for some years there was debate over whether it represented a significant product of lipid oxidation in vivo. There is now a substantial body of evidence supporting its generation by lipid oxidation [14,37,38], although the mechanism for its formation remains unclear. There are reports of it being formed from ω-6 unsaturated fatty acids, but that the yield is higher from ω-3 unsaturated fatty acids and increases with increasing number of double bonds [39].…”

“…Larger increases have been reported for hexanal and heptanal in lung cancer and acrolein in diabetics. However, care needs to be taken in interpreting increases in acrolein concentration as it may come from sources other than lipid oxidation, such as the catabolism of threonine and spermidine or the oxidation of sugars [37].…”

“…Formed via 15-hydroperoxyeicosatetraenoic acid 15-HpETE (from arachidonic acid) and from 13-hydroperoxy-octadecadienoic acid 13-HpODE (from linoleic acid). [37,144] 4-hydroperoxy-2-nonenal (HpNE) C9…”

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

“…Humans are exposed to acrolein via cigarette smoke, wood, plastic, overheated cooking fats and drinking water [12][13][14]. In addition to exogenous sources of exposure, acrolein is produced in situ during the normal catabolism of various amino acid and also is a toxic metabolite of cyclophosphamide, an anti-cancer drug [13]. Acrolein is a strong electrophile, and therefore, shows high reactivity with various bio-molecules including proteins, DNA and glutathione [15][16][17].…”