Kinetic and density functional theory (DFT) studies of in vitro reactions of acrylamide with the thiols: captopril, l-cysteine, and glutathione

Abstract

In vitro kinetic studies with DFT computations to explain the potential of acrylamide metabolism/toxicity with thiols in vivo.

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

“…As a first step, these reactions were analyzed experimentally at different temperatures and a pH of 7.3 in order to observe their behavior ( Figure 2 ). The data were adjusted to a pseudo-first-order reaction (R > 0.9542), and similar performance has been described with respect to ACR in this type of reaction [ 10 ]. From this information, the reaction rate constants were calculated, obtaining higher reaction constants with L-GSH than L-Cys ( Table 1 ).…”

“…From this information, the reaction rate constants were calculated, obtaining higher reaction constants with L-GSH than L-Cys ( Table 1 ). The pseudo-first-order rate constants were affected by the pH level because reactions between ACR and thiols improve when the pH increases above 7.0 [ 10 , 11 ]. In addition, the activation energy (Ea), calculated by the Arrhenius equation, was 62.19 and 30.05 for the L-Cys-ACR and L-GSH-ACR reactions, respectively.…”

“…This analysis was centered on the nature of bond breaks, followed by the formation of Michael adducts [ 10 ] with stabilization by the migration of the hydrogen from sulfur to -carbon. This step of the mechanism was analyzed by two pathways (radical and ionic) following the approximation of the transition state with the isolated species in order to find out the electronic nature of the hydrogen migration and understand the kinetics in the formation of Michael adducts.…”

Towards a Deeper Understanding of the Mechanisms of Interaction between Acrylamide and Key Body-Fluid Thiols

“…Normal cell concentration of GSH is 5 mM [15]. Only AA and GA that cross the blood-brain barrier can cause toxic effects [17]. If GSH concentration is already low due to illness or malnutrition, then the possibility of AAinduced toxicity will be greater.…”

“…It is generally accepted that AA (and similarly GA) react with amines and thiols via Michaeladdition ( Figure 1) [7]. As such, our group has investigated the reaction rates between AA and the thiols captopril (CapSH), Lcysteine (CySH), and GSH [17,21] which are commonly found in body-fluids. L-cysteine and GSH are naturally occurring thiols within the body.…”