Identification of Mouse CYP2C Involved in Arachidonic Acid

目的是鉴定小鼠体内的细胞色素P2蛋白， 确定它们对内源代谢的贡献 花生四烯酸和维甲酸(维生素A)等化合物 并确定它们对药物新陈代谢的贡献 环境化学品，如用于生物检测的化学品。至 确定在哪些组织中发现了这些酶，以及 内源化合物的这些变化在人体内的重要性 生理和病理过程的过程。最终 将产生特定的基因敲除小鼠来测试 生理学中的这些途径及其在 环境化学物质的代谢。成就 我们已经在小鼠体内鉴定了五个细胞周期蛋白P2 C，其中包括四个新的 细胞色素P450酶C。这是一种常见的毒性和毒性实验动物 致癌性测试。我们在c DNA中表达了全部5个细胞色素P2 C 表达系统，并比较它们的代谢能力 人们正在将花生四烯酸与人类的花生四烯酸进行比较。 CYP2C29是主要的形式，主要产生14，15 环氧二十碳三烯酸(EET)。此外，还发现了细胞色素P4502C29的mRNA 肺、肝、脑、肾、心、肠。CYP2C39还 生产了14，15个EET。产生的1，12-EET基因是 发现于肝、脑、肾和肠道。CYP2C40产生了一种 未知羟基二十碳四烯酸(16、17或18-HETE) 在大脑、肾脏和肠道中也发现了这种物质。.的存在 这些酶中的一些在肝外组织中，如肺和 冒号暗示了它们在生理上的重要性。 器官。

AIMS To identify the CYP2Cs in the mouse, establish their contribution to the metabolism of endogenous compounds such as arachidonic acid and retinioic acid (Vitamin A) and to establish their contribution to the metabolism of drugs and environmental chemical such as those used in bioassays. To determine which tissues these enzymes are found in, and the importance of these changes in endogenous compounds in physiological and pathological processes process. Eventually specific knockout mice will be generated to test the importance of these pathways in physiology and their importance in the metabolism of enviromental chemicals. ACCOMPLISHMENTS We have identified five CYP2Cs in the mouse, including four new CYP2Cs. This is a common laboratory animal for toxicity and carcinogenicity tests. We expressed all five CYP2Cs in cDNA expression systems and compared their ability to metabolize arachidonic acid is being compared with that of the human forms. CYP2C29 was the predominant form and produced primarily 14,15 epoxyeicosatrienoic acid (EET). CYP2C29 mRNA was also found in lung, liver, brain, kidney, heart and intestine. CYP2C39 also producued 14,15 EET. CYP2C38 produced 1,12-EET mRNA was found in liver brain, kidney and intestine. CYP2C40 produced an unidentified hydroxyeicosatetraenoic acid (16, 17, or 18-HETE) and was also found in brain, kidney and intestine. The presence of some of these enzymes in extrahepatic tissues such as lung and colon suggests their importance in physiological roles in these organs.