测定咖啡因代谢物评价N-乙酰转移酶、CYP1A2和黄嘌呤氧化酶活性  

DETERMINATION OF CAFFEINE METABOLITE FOR THE EVALUATION OF N ACETYLTRANSFERASE, CYP1A2 AND XANTHINE OXIDASE ACTIVITIES *

作　　者：卢建丰[1] 易涛[1] 曹晓梅[1] 卓海通[1] 凌树森[1] 

机构地区：[1]南京军区南京总医院临床药理科

出　　处：《药学学报》1997年第11期813-818,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：目的是对中国人Ｎ乙酰化酶（ＮＡＴ２）、ＣＹＰ１Ａ２酶和黄嘌呤氧化酶（ＸＯ）的活性进行分析。１２０名健康志愿者饮用３杯咖啡后于４～５ｈ留尿，用ＨＰＬＣ方法测定尿中５种咖啡因主要代谢物浓度，即５乙酰胺基６甲酰胺基３甲基尿嘧啶（ＡＦＭＵ）、１甲基黄嘌呤（１Ｘ）、１甲基尿酸（１Ｕ）、１，７二甲基尿酸（１７Ｘ）、１，７二甲基黄嘌呤（１７Ｕ）。其中Ｎ乙酰化酶活性用ＡＦＭＵ／１Ｘ或ＡＦＭＵ／（ＡＦＭＵ＋１Ｘ＋１Ｕ）表示；ＣＹＰ１Ａ２酶活性指标采用（ＡＦＭＵ＋１Ｘ＋１Ｕ）／１７Ｘ或ＡＦＭＵ＋１Ｘ＋１Ｕ）／１７Ｕ；ＸＯ酶活性指标采用１Ｕ／１Ｘ或１Ｕ／（１Ｘ＋１Ｕ）。结果表明，Ｎ乙酰化酶活性呈两态分布，慢代谢者占１６７％，ＣＹＰ１Ａ２和ＸＯ酶活性呈对数正态分布，其代谢比值与国外文献报道一致。提示通过测定咖啡因代谢物比值，可以进行ＮＡＴ２酶、ＣＹＰ１Ａ２酶和黄嘌呤氧化酶活性分析。Caffeine was used as a metabolic probe to measure, in 120 healthy volunteers, the activities of three enzymes, deduced to be N acetyltransferase(NAT2), CYP1A2 and xanthine oxidase(XO). The caffeine metabolites of 5 acetylamino 6 formylamino 3 methyluracil(AFMU), 1 methylxanthine(1X), 1 methyluric acid(1U), 1,7 dimethylxanthine(17X), and 1,7 dimethyluric acid(17U) in urine were determined with HPLC after 4～5 hours of caffeine drink. The ratios of AFMU/1X or AFMU/(AFMU+1X+1U), (AFMU+1X+1U)/17X or (AFMU+1X+1U)/17U, and 1U/1X or 1U/(1X+1U) were used as the index of NAT2, CYP1A2, and XO activities respectively. Frequency distribution analysis of the metabolic ratios of NAT2 indicated two distinct group with 20 slow acetylators and 100 rapid acetylators. Similar CYP1A2 activity was found in Chinese compared with European volunteers. Frequency analysis of CYP1A2 indicated the log normal distribution in 120 Chinese. The CYP1A2 index was much higher in smokers than that in non smokers. But no obvious difference was observed between young and old volunteers. The XO index also showed log normal distribution and has the similar value compared with European volunteers. The concentration variations of 1X and 1U in young volunteers were much lower than that in old volunteers.

关 键 词：咖啡因 N-乙酰化酶 CYP1A2酶 黄嘌呤氧化酶 

分 类 号：R971.7[医药卫生—药品]