A DFT Study of the Reaction of Acrylamide with L-Cysteine and L-Glutathione

Abstract

Thermal processing of certain foods implies the formation of acrylamide, which has been proven to provoke adverse effects on human health. Thus, several strategies to mitigate it have been developed. One of them could be the application of organosulfur compounds obtained from natural sources to react with the acrylamide, forming non-toxic adducts. A DFT study of the acrylamide reaction with the organosulfur model compounds L-cysteine and L-glutathione by Michael addition and a free radical pathway complemented by a kinetic study of these model molecules has been applied. The kinetic evaluation results demonstrate that the L-glutathione reaction exhibited a higher rate constant than the other studied compound.

Reactivity of Acrylamides Causes Cytotoxicity and Activates Oxidative Stress Response

“…It is known that acrylamides react with GSH via a Michael addition. ,, The resulting Michael adducts were identified as common metabolites of acrylamides, making the reaction with GSH an important detoxification process of acrylamides in vivo . , Mass spectrometry was used to identify the transformation products of the reaction with GSH. As expected, Michael conjugation products with GSH were found for eight test chemicals.…”

“…The toxicity of reactive chemicals exceeds baseline toxicity (narcosis), which is the lowest toxicity a chemical can have and is caused by the incorporation of the chemicals into the cell membrane . Reactive chemicals are of special concern since they usually have 10 to 10,000 times higher toxicity than baseline toxic chemicals, and their toxicity can have different modes of action (MOA), but is mostly triggered by irreversible reactions with thiol, amino, or hydroxyl groups of biological nucleophiles such as proteins, peptides, and DNA. − The reaction of acrylamides with nucleophiles is a Michael addition where the α,β-unsaturated carbonyl moiety of the acrylamide acts as the Michael acceptor and the biological nucleophile acts as the Michael donor. , Especially the tripeptide glutathione (γ- l -glutamyl- l -cysteinyl-glycin, GSH) is a target of reactive chemicals since it has a free thiol group and is present in large amounts in the cell (Figure ). Acrylamide can also be metabolized by cytochrome P450 2E1 to its metabolite glycidamide, which reacts with DNA bases and causes genotoxicity (Figure ).…”

“… 14 − 16 The reaction of acrylamides with nucleophiles is a Michael addition where the α,β-unsaturated carbonyl moiety of the acrylamide acts as the Michael acceptor and the biological nucleophile acts as the Michael donor. 17 , 18 Especially the tripeptide glutathione (γ- l -glutamyl- l -cysteinyl-glycin, GSH) is a target of reactive chemicals since it has a free thiol group and is present in large amounts in the cell ( Figure 1 ). 19 Acrylamide can also be metabolized by cytochrome P450 2E1 to its metabolite glycidamide, which reacts with DNA bases and causes genotoxicity ( Figure 1 ).…”