IMMUNOPURIFICATION AND CHARACTERIZATION OF CYTOCHROME P-450

细胞色素P-450代谢一系列化合物， 包括药物和致癌物等外来生物，以及 内源性化合物，如类固醇。这个项目的重点是 是结构-功能关系的表征和 这种酶的多种形式的调节。单克隆 大鼠P-450的抗体(MAb)是这些研究中的一个工具。A 3- 甲基胆蒽(MC)诱导的P-450蛋白免疫纯化 从老鼠的肝脏和肺中提取。以氨基酸为基础 序列分析、肽图谱和分子量， 肝P-450和肺P-450难以区分。使用单抗来 乙醇诱导的大鼠肝脏P-450，一种P-450已从 无论是大鼠肝脏还是人类肝脏。它们在一级结构上的不同之处在于 由不同的氨基末端序列和多肽证明 地图。研究P-450的发育调控。 3-和24-P-450依赖的睾酮代谢研究 一个月大的老鼠。环羟化模式，以及 肝脏构成P-450，随年龄变化。而P-450的活性 随着年龄的增长，7α-羟基酶和 负责这项活动的相应P-450表格增加 随着年龄的增长。

The cytochromes P-450 metabolize a wide array of compounds, including xenobiotics such as drugs and carcinogens, and endogenous compounds such as steroids. The focus of this project is the characterization of structure-function relationships and regulation of the multiple forms of this enzyme. Monoclonal antibodies (MAbs) to rat P-450s are a tool in these studies. A 3- methylcholanthrene (MC)-inducible P-450 was immunopurified from the livers and lungs of rats. On the basis of amino acid sequence analysis, peptide mapping, and molecular weight, the liver and lung P-450s were indistinguishable. Using a MAb to ethanol-inducible rat liver P-450, a P-450 has been purified from both rat and human liver. These differed in primary structure as evidenced by different amino terminal sequences and peptide maps. Developmental regulation of P-450 was examined by studying P-450-dependent testosterone metabolism in 3- and 24- month old rats. Ring hydroxylation patterns, as well as content of liver constitutive P-450s, varied with age. While P-450 activities generally declined with age, the 7 alpha-hydroxylase and corresponding P-450 form responsible for this activity increased with age.