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  本文選題：細(xì)胞色素P4502E1(CYP4502E1)　切入點：單核苷酸多態(tài)性(SNP)　出處：《中國醫(yī)科大學(xué)》2005年碩士論文　論文類型：學(xué)位論文

【摘要】：前言 細(xì)胞色素P450酶系(Cytochrome P450,CYP450)是一組結(jié)構(gòu)和功能相關(guān)的超家族基因編碼的同工酶,其特征是與CO結(jié)合后在450nm處有吸收峰的含血紅素的單鏈蛋白質(zhì)。在人類CYP450超基因家族中,主要有三個基因家族CYP4501、CYP4502及CYP4503在體內(nèi)參與外源生物轉(zhuǎn)化,并已發(fā)現(xiàn)人類肝臟中至少有19種CYP450酶參與藥物的代謝。大量研究表明,人體內(nèi)許多藥物的代謝存在個體差異,這種差異可能是由遺傳和后天雙重因素所致。CYP450的合成受著遺傳基因的調(diào)控,一旦基因發(fā)生變異,它所調(diào)控合成的CYP450酶及酶所催化的藥物代謝即發(fā)生變化。因此CYP450酶的多態(tài)性是構(gòu)成藥物代謝種族及個體差異的基礎(chǔ)。已知在人類的CYP450酶系統(tǒng)中具有遺傳多態(tài)性的有CYP4501A1、CYP4501A2、CYP4502A6、CYP4502C、CYP4502D6、CYP4502E1及CYP4503A4等,其中研究比較多的是CYP4502E1。 CYP4502E1是二甲基亞硝胺D-脫甲基酶,它主要參與激活小分子致癌物如苯、四氯化碳和亞硝胺等,同時參與酒精的氧化代謝和產(chǎn)生自由基而啟動脂質(zhì)過氧化過程。CYP4502E1主要存在于肝臟,在食管和肺組織也有表達(dá)。雖然CYP4502E1受外界因子如酒精的誘導(dǎo),但不論是誘導(dǎo)前或誘導(dǎo)后其活性水平都有相當(dāng)大的個體差異,提示其表達(dá)是由遺傳決定的。許多研究表明CYP4502E1基因多態(tài)性與其代謝活性密切相關(guān),并與某些癌癥的易感性相關(guān)。 CYP4502E1基因位于第10號染色體,共有9個外顯子和8個內(nèi)含子,計11413個堿基。目前報道有5種限制性片段長度多態(tài)性(restrict fragment length polymorphism,RFLP)位點,即TaqI、DraI、RsaI、MspI及5′端的RsaI/PstI。其中DraI和5′端Rsal/PstI將影響CYP2E1的表達(dá)。DraI多態(tài)性位點
[Abstract]:Foreword. Cytochrome P450 (Cytochrome P450) is a group of structural and functional related superfamily genes encoding isozymes characterized by a heme-containing single-stranded protein with a absorption peak at 450 nm after CO binding. Three major gene families, CYP4501CYP 4502 and CYP4503, are involved in exogenous biotransformation in vivo, and at least 19 CYP450 enzymes have been found to be involved in the metabolism of drugs in the human liver. A large number of studies have shown that there are individual differences in the metabolism of many drugs in the human body. This difference may be caused by both genetic and acquired factors. The synthesis of CYP450 is regulated by genetic genes, and once the genes are mutated, Therefore, the polymorphism of CYP450 enzyme is the basis of the racial and individual differences in drug metabolism. It is known that CYP4501A1, CYP4502A2, CYP4502A6, CYP4502CCYP4502D6, CYP4502E1 and CYP4503A4, are known to have genetic polymorphisms in the human CYP450 enzyme system. CYP4502E1. CYP4502E1 is a D- demethylase of Dimethylnitrosamine, which is mainly involved in the activation of small carcinogens such as benzene, carbon tetrachloride and nitrosamine, and in the oxidative metabolism of alcohol and the production of free radicals. CYP4502E1 is mainly present in the liver. Although CYP4502E1 is induced by external factors such as alcohol, its activity levels vary considerably before and after induction. Many studies have shown that the polymorphism of CYP4502E1 gene is closely related to its metabolic activity and associated with the susceptibility of some cancers. The CYP4502E1 gene is located on chromosome 10, with 9 exons and 8 introns. There are 5 restriction fragment length polymorphisms, strict fragment length polymorphisms, RFLPs. The Rsai / PstI of the 5 'end and the RsaI / PST I of the 5' end of Taq Igna Drai, in which DraI and 5 'end Rsal/PstI will affect the expression of CYP2E1. Drai polymorphism.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2005
【分類號】：D919.1

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