白杨素在人小肠S9中磺酸化结合反应的代谢特性  

Metabolism profile of sulfation of chrysin in human small intestine S9

作　　者：蒋昆谕[1] 周一平[1] 马颖林 周昱[1] 张懋璠 孟胜男[1] 

机构地区：[1]中国医科大学药学院药剂教研室,辽宁沈阳110122

出　　处：《中国生化药物杂志》2015年第4期154-157,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81173123);辽宁省自然科学基金课题(2013021080)

摘　　要：目的研究白杨素分别与人重组酶SULT1A3和人小肠S9(human small intestine S9,HSI S9)孵育体系磺酸化结合反应的代谢特性。方法采用高效液相色谱法,测定白杨素及其代谢产物,并应用LC-MS/MS液质联用技术鉴定其结构。分别建立白杨素与重组酶SULT1A3及与人小肠S9的反应体系,测定不同浓度的白杨素在不同酶反应中的代谢速率。结果白杨素与SULT1A3及人小肠S9孵育体系反应的代谢产物均为单磺酸化结合产物。白杨素与重组酶SULT1A3及人小肠S9的酶反应均呈双相动力学特征。白杨素与SULT1A3酶反应的动力学参数Km为(3.06±1.04)、(0.41±0.06)μM,Vmax为(12.13±1.30)、(6.72±1.61)nmol/(min·mg),Vmax/Km为3.96、16.39 mL/(min·mg)。白杨素与人小肠S9的酶反应的动力学参数Km为(1.92±0.35)、(0.01±0.00)μM,Vmax为(0.52±0.02)、(0.08±0.02)nmol/(min·mg),Vmax/Km为0.27、8.00 mL/(min·mg)。重组酶SULT1A3和人小肠S9分别介导的白杨素磺酸化结合反应的代谢呈现显著的相关性(R2=0.985)。结论 SULT1A3在白杨素的肠道代谢中发挥主导作用,小肠可能是白杨素的主要代谢器官。Objective To investigate the metabolic profile of chrysin in SULT1A3 and human small intestine S9.Methods After incubation of chrysin using in vitro SULT1A3 and human small intestine S9 system, high-performance liquid chromatography was utilized to determine the sulfates of chrysin.Mass spectrum（MS） were employed to elucidate the structures of metabolite.Results In the SULT1A3 with PAPS, Km were （3.06 ±1.04） and （0.41±0.06） μM, Vmax were （12.13 ±1.30） and （6.72 ±1.61） nmol/（min· mg）, Vmax/Km were 3.96 and 16.39 mL/（min· mg）, respectively.In the human small intestine S9 with PAPS, Km were （1.92 ±0.35） and （0.01 ±0.00） μM, Vmax were （0.52 ±0.02） and （0.08 ± 0.02） nmol/（min· mg）, Vmax/Km were 0.27 and 8.00 mL/（min· mg）.The metabolic behavior of chrysin in SULT1A3 and human small intestine S9 both were followed biphasic kinetics.The sulfation of chrysin in SULT1A3 showed a significant correlation with that in human small intestine S9（R^2 =0.985）.Conclusion The result indicates that SULT1A3 is the major enzyme to the metabolism of chrysin, human small intestine may be the main metabolic organs of chrysin.

关 键 词：白杨素 SULT1A3 人小肠S9 磺酸化结合反应 

分 类 号：R944[医药卫生—药剂学]