活性羰基物质诱导肉制品中2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）形成机理

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is easy to generate in meat products with high temperature treatments, which has strong impact on meat safety. Classical theory holds that free radicals can promote PhIP formation, however the project team early research found that reactive carbonyls species also has strong impact on PhIP formation, but the mechanism of PhIP formation in meat products induced by reactive carbonyls species is not clear. So the aim of this project is to identify and separate the lipid-derived reactive carbonyl species by the thermally induced tests of intramuscular fat vitro model and the multistage mass spectrometry; and then to reveal the chemical structures and reactions of the reactive carbonyl species inducing PhIP formation after figuring out the formation rules and reactions rate changes of PhIP induced by reactive carbonyl species by the thermally induced tests of orthotopic recombination muscle model, phenylalanine+creatine model, the Strecker degradation model and aldol condensation model in PhIP formation pathway; and finally to reveal the interaction molecules and their group binding sites in induced reactions mediated by reactive carbonyl species after finding out reaction kinetics, intermediates evolution, and molecular binding dynamic change by reaction kinetics analysis and Discovery Studio techniques; eventually to reveal the mechanism of PhIP formation in meat products induced by reactive carbonyls species, so as to provide new control technology for PhIP in meat products.

高温加工肉制品易产生2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP），影响肉制品安全。经典理论认为自由基促进PhIP形成，而项目组前期研究发现活性羰基物质也能诱导PhIP形成，但具体机理尚不清楚。本项目基于肌内脂肪离体模型的热诱导试验和多级质谱学方法，鉴定脂质衍生的活性羰基物质；采用原位重组肌肉模型和“苯丙氨酸+肌酸”模型以及PhIP形成通路中斯特勒克降解和醇醛缩合模型的热诱导试验，研究活性羰基物质诱导PhIP形成规律和反应速率变化，确证诱导PhIP形成的活性羰基物质结构及其诱导的反应；利用反应动力学和Discovery Studio分子建模等技术，研究活性羰基物质诱导PhIP形成反应的动力学和中间体物质演变以及分子对接动态变化，解析活性羰基物质诱导PhIP形成反应的分子互作对象和基团位点，揭示活性羰基物质诱导肉制品中PhIP形成机理，为研发PhIP控制新技术提供理论参考。

烧烤肉制品深受全世界人民喜爱，但高温加工下形成的潜在致癌物PhIP影响人民健康。项目以烤羊肉为研究对象，鉴定分离肌内脂肪热诱导产生的活性羰基物质（RCSs），研究了诱导PhIP形成的RCSs主要为甲醛和丙烯醛；确证了苯丙氨酸Strecker降解和肌苷酸与苯乙醛缩合为RCSs介导PhIP形成的主要化学反应；阐明了诱导反应中RCSs攻击苯丙氨酸α-C，活化苯丙氨酸，促进其斯特勒克（Strecker）降解；攻击肌酸酐2-NH2，活化肌苷酸，促进其与苯乙醛缩合，从而诱导PhIP形成的分子机理。确证了RCSs为诱导烤肉加工过程中杂环胺形成的关键内源因子，为研发烤肉中PhIP靶向控制技术做了重要铺垫。

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