The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine
NNK is considered to be the most carcinogenic compound of the four TSNAs and necessary to be metabolically activated to exert its carcinogenic effect to human.For the simultaneous intake of NNK and other compounds with similar molecular structure in the context of tobacco smoke,whether NAT,NAB and nicotine contribute to the inhibitory potency of CYP P450 enzyme-catalyzed NNK metabolism or not needs to be investigated.In the in vitro study,OPB,HPB and OPBA were established as the products of CYP2A13-catalyzed NNK metabolism and kinetic parameters were calculated from Michaelis-Menten equation.Addition of NAT,NAB or nicotine resulted in a competitive inhibition for NNK metabolism catalyzed by CYP2A13.The inhibition constant Ki value was calculated as 0.21 μM(NAT),0.23 μM(NAB)and 8.51 μM(nicotine)for OPB formation,0.71 μM(NAT),0.87 μM(NAB)and 25.01 μM(nicotine)for HPB formation,0.36 μM(NAT),0.50 μM(NAB)and 6.57 μM(nicotine)for OPBA formation,respectively.In addition,the study of transformation of three metabolites firstly revealed OPB was not only an end product but also an intermediate product of CYP2A13-catalyzed NNK metabolism.These results suggest that structurally similar tobacco constitutes with weak or no carcinogenicity influence the metabolic activation of NNK,which interfere in its carcinogenicity to some extent.
Xingyu Liu Jie Zhang Chen Zhang Bicheng Yang Limeng Wang Jun Zhou
Shanghai Tobacco Group Corporation,99 Wansheng South Street,Tongzhou District,Beijing 101121,China Jiangxi Provincial Maternal And Child Health Hospital,318 Bayi Road,Nanchang 330006,Jiangxi,China Dalian Institute of Chemical Physics,University of Chinese Academy of Sciences,457 Zhongshan Road,Da
国内会议
北京
英文
1-17
2016-11-01（万方平台首次上网日期，不代表论文的发表时间）