Computational Study On The Maillard Reaction Mechanism Of Glycine With Glucose And The Inhibition Mechanism Of Methylglyoxal

Maillard reaction is a process in which proteins and carbohydrates react to produce melanin and various intermediates under heating conditions,which occurs in many processed foods.Generally speaking,heat-processed food can make food with attractive color and aroma,but due to the high temperature conditions,it will produce some carcinogenic harmful substances,such as heterocyclic amines,acrylamide,advanced glycation end products,etc.In order to control the formation of these harmful products,it is necessary to study the Maillard reaction process and mechanism,so as to understand the formation process of harmful products and their intermediates.At present,most studies have explored the inhibitory effect and inhibition rate of these inhibitors by adding various inhibitors to inhibit the formation of harmful products,but there are few studies on their inhibition mechanism and the specific reaction process is not clear.Therefore,in this paper,the reaction mechanism of Maillard reaction in the primary and intermediate stages was discussed by using density functional theory（DFT）with glycine and glucose as models.Then,the reaction mechanism and structure of three natural flavonoids with MGO were studied.Finally,the reaction mechanism,reactivity and sites of four vitamins with MGO were studied.The specific research contents and results are as follows:1.Using glycine and glucose as models,the DFT method was used to calculate the transition state,structure optimization and activation energy of each elementary reaction in the reaction route,and the specific mechanism of the primary and intermediate Maillard reaction was discussed in depth.The results showed that the basic reaction process in the primary stage is the condensation of amino group and carbonyl group to form Schiff base,and then Schiff base undergoes two proton transfer through tautomerism to form Amadori rearrangement product.In the intermediate stage,the two main reaction pathways of 1-2 and 2-3 enolization were comprehensively investigated.The first pathway produces 5-hydroxymethylfurfural（5-HMF）through isomerization,dehydration,hydrolysis,elimination and condensation,and the activation energy ranges from 15.0 to 55.0 kcal mol^-1.In the second pathway,dicarbonyl compounds were formed by isomerization and elimination,and then aldehyde compounds were formed by Strecker degradation condensation,decarboxylation,hydrolysis and condensation.The activation energy of the reaction varied greatly from 0.2 to 55.0 kcal mol^-1.The results show that both pathways are involved in complex reactions,some are low barrier reactions,and some are high barrier reactions.It is worth pointing out that the water catalytic process is very critical,which exists in most processes and can effectively reduce the reaction energy barrier.2.The specific mechanism of three flavonoids（quercetin,baicalein,liquiritigenin）inhibiting MGO reaction was discussed in depth.The results showed that these three flavonoids may affect the formation of MGO from three ways:nucleophilic addition reaction,aldol condensation and tautomerism.The nucleophilic addition reaction is that the C atom on the flavonoid A ring reacts with the C atom of the MGO terminal carbonyl group to form a C-C bond,and the activation energy reaches more than 40 kcal mol^-1.The aldol condensation is that the O atom of-OH on the A ring of flavonoids reacts with the C atom of the carbonyl group at the MGO end to form an O-C bond,and the reaction activation energy is about 20 kcal mol^-1.The tautomerism affects the nucleophilic addition and aldol condensation reactions through the proton transfer of-OH and=O.It can be seen from the calculated energy that the activation energy required for the path of aldol condensation is the lowest,indicating that these three flavonoids may be more inclined to undergo aldol condensation reaction to capture MGO.The nucleophilic addition reaction needs to be carried out at high temperature,and the occurrence of tautomerism enhances the activity of quercetin and baicalein to capture MGO by nucleophilic addition reaction.3.The mechanism of four vitamins（thiamine,nicotinic acid,pyridoxine and ascorbic acid）inhibiting MGO reaction and their reaction sites and activities were studied.The calculation results showed that the reaction of these four compounds with MGO can be divided into two ways:carbonyl ammonia condensation and aldol condensation.The calculated activation energy of each reaction showed that the occurrence of carbonyl ammonia reaction requires two steps:condensation and dehydration reaction,and dehydration reaction is the rate-determining step.The activationenergyoftherate-determiningstepof4-amino-5-hydroxymethyl-2-methylpyrimidine and VB6 is 36.5 kcal mol^-1 and 28.5kcal mol^-1,respectively.At the same time,the four compounds are more inclined to react with MGO in the way of aldol condensation,and the activation energy is about 16～25 kcal mol^-1;compared with the other three compounds,the activation energy of the aldol condensation reaction of pyridoxine is lower.The energy difference between HOMO and LUMO of pyridoxine is the lowest,and the reactivity of pyridoxine is the strongest.