人肝微粒体中茶碱代谢的表征
Characterisation of theophylline metabolism in human liver microsomes.
作者信息
Robson R A, Matthews A P, Miners J O, McManus M E, Meyer U A, Hall P M, Birkett D J
机构信息
Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, S.A., Australia.
出版信息
Br J Clin Pharmacol. 1987 Sep;24(3):293-300. doi: 10.1111/j.1365-2125.1987.tb03172.x.
Abstract
- A radiometric high performance liquid chromatographic method is described for the assay of theophylline metabolism in vitro by the microsomal fraction of human liver. 2. Formation of the three metabolites of theophylline (3-methylxanthine, 1-methylxanthine and 1,3-dimethyluric acid) were linear with protein concentrations to 4 mg ml-1 and with incubation times up to 180 min. 3. The coefficients of variation for the formation of 3-methylxanthine, 1-methylxanthine and 1,3-dimethyluric acid were 1.2%, 1% and 1.6%, respectively. 4. Theophylline is metabolised by microsomal enzymes with a requirement for NADPH. 5. The mean (n = 7) Km values for 1-demethylation, 3-demethylation and 8-hydroxylation were 545, 630 and 788 microM, respectively, and the mean Vmax values were 2.65, 2.84 and 11.23 pmol min-1 mg-1, respectively. 6. There was a high correlation between the Km and Vmax values for the two demethylation pathways suggesting that the demethylations are performed by the same enzyme. 7. Overall the in vitro studies are consistent with the in vivo results which suggest the involvement of two cytochrome P-450 isozymes in the metabolism of theophylline.
摘要
- 描述了一种放射性高效液相色谱法，用于通过人肝脏微粒体部分体外测定茶碱代谢。2. 茶碱的三种代谢产物（3-甲基黄嘌呤、1-甲基黄嘌呤和1,3-二甲基尿酸）的形成与蛋白质浓度在4mg/ml以内以及孵育时间长达180分钟呈线性关系。3. 3-甲基黄嘌呤、1-甲基黄嘌呤和1,3-二甲基尿酸形成的变异系数分别为1.2%、1%和1.6%。4. 茶碱由微粒体酶代谢，需要NADPH。5. 1-去甲基化、3-去甲基化和8-羟基化的平均（n = 7）Km值分别为545、630和788μM，平均Vmax值分别为2.65、2.84和11.23pmol min-1 mg-1。6. 两种去甲基化途径的Km和Vmax值之间存在高度相关性，表明去甲基化由同一种酶进行。7. 总体而言，体外研究与体内结果一致，提示两种细胞色素P-450同工酶参与茶碱代谢。
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