The investigation of kenitics of UGT1A1 enzyme in different system on the basic of Bilirubin metabolites / 中国药学杂志

ABSTRACT

OBJECTIVE: To detect the kenitics of UGTIAI enzyme in three different systems. METHODS: A UPLC-MS/MS method was developed to measure the bilirubin. RESULTS: Glucuronidation kinetic constants were analyzed by fitting the Michaelis-Menten equation.As shown in our study, the apparent kinetic parameters of total bilirubin glucuronides were; KRLM>KHLM≈KrUGT1A1LM, VRLM≈VHLM>VrUGT1A1, CLHLM>CLrUGT1A1LM≈CLrRLM indicated that rUGT1A1 had the strongest binding affinity to bilirubin but could not convert it to bilirubin glucuronidations immediately.On the contrary RLM had a weaker binding affinity to the bilirubin, but could conver it rapidly. CONCLUSION: Compared the kinetic in the different systems we could find that HLM almost had the same Km as rUGT1A1 which demonstrated the UGTIAI enzyme was the primary enzyme mediating the metabolism of bilirubin.The difference parameter between three systems is attributed to the species differences.Summarily our study supplies experimental basis for the further