Gorodischer R, Yaari A, Margalith M, Warszawski D, Ben-Zvi Z
Biochem Pharmacol. 1986 Sep 15;35(18):3077-81. doi: 10.1016/0006-2952(86)90389-8.
The metabolism of theophylline was studied in liver slices of young and adult rats. Theophylline and six metabolite fractions were recognized in adult liver by thin-layer radiochromatography and high performance liquid chromatography: 1-methyluric acid; 1-methylxanthine; 1,3-dimethyluric acid and/or 3-methylxanthine; caffeine; a uracil derivative and two unknown polar compounds. Preincubation with caffeine or theobromine inhibited theophylline metabolism. Allopurinol decreased the formation of three metabolite fractions but markedly increased the production of 1-methylxanthine. SKF 525-A inhibited the overall metabolism of theophylline. The specific activity of the enzyme system was 3.2 +/- 0.4 nmoles X (g liver)-1 X hr-1 in the 4- to 5-day-old rat and increased to a peak of 25.7 +/- 1.7 in the 28-day-old; values for Km and Vmax in the 7- and 28-day-olds were 132.1 and 67.5 microM, and 23.9 and 52.1 nmoles X (g liver)-1 X hr-1 respectively. Theophylline and the same six metabolites were identified in young and adult rats, but the development pattern was not uniform. Peak age-related activity and involvement of mixed-function oxidase system are features which are common to theophylline and caffeine metabolism. Xanthine oxidase played a role in theophylline metabolism. Formation of caffeine from theophylline was not dependent on a lack of activity of other pathways.
在幼年和成年大鼠的肝切片中研究了茶碱的代谢。通过薄层层析放射色谱法和高效液相色谱法在成年肝脏中识别出茶碱和六种代谢物组分：1-甲基尿酸；1-甲基黄嘌呤；1,3-二甲基尿酸和/或3-甲基黄嘌呤；咖啡因；一种尿嘧啶衍生物和两种未知的极性化合物。用咖啡因或可可碱预孵育可抑制茶碱代谢。别嘌呤醇减少了三种代谢物组分的形成，但显著增加了1-甲基黄嘌呤的产生。SKF 525-A抑制了茶碱的整体代谢。在4至5日龄大鼠中，酶系统的比活性为3.2±0.4纳摩尔×（克肝脏）-1×小时-1，并在28日龄时增加到峰值25.7±1.7；7日龄和28日龄大鼠的Km和Vmax值分别为132.1和67.5微摩尔，以及23.9和52.1纳摩尔×（克肝脏）-1×小时-1。在幼年和成年大鼠中鉴定出茶碱和相同的六种代谢物，但发育模式并不一致。与年龄相关的峰值活性和混合功能氧化酶系统的参与是茶碱和咖啡因代谢共有的特征。黄嘌呤氧化酶在茶碱代谢中起作用。由茶碱形成咖啡因并不依赖于其他途径缺乏活性。
