效应的两个人类CYP1B1基因突变,G61E和R469W稳定和内源性类固醇代谢基质。

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简颂我Stoilov我Sarfarazi M, Schenkman简森-巴顿

效应的两个人类CYP1B1基因突变,G61E和R469W稳定和内源性类固醇代谢基质。

药物基因学。2001;12月11 (9):793 - 801。

PubMed ID

11740343 (在PubMed

]

文摘

CYP1B1与眼睛的正常发展的疾病表型,原发性先天性青光眼(PCG)。CYP1B1 mRNA表达人类胎儿组织的互补脱氧核糖核酸库,支持其参与组织发展的建议。最高表达水平被发现在胸腺和肾、脾紧随其后。大大降低水平观察肺、心脏和骨骼肌。没有检测到表达肝细胞或脑细胞。CYP1B1能够代谢类固醇激素。睾酮是一个可怜的衬底和活动与孕酮高6倍,但雌二醇是首选的衬底,表现出更大的代谢物轮廓与CYP1B1 CYP1A2。主要代谢产物环羟基化(75 - 80%)。人15α- 6α- 16α- 6 beta-hydroxy代谢物。两个CYP1B1基因突变在家庭的首选表型不完全外显率是在大肠杆菌表达。 G61E, a hinge region mutation, and R469W, a heme region mutation, were shown to code for holoenzymes. G61E had greatly diminished stability, while the R469W holoenzyme, if anything, was stabilized. Both mutants showed compromised catalytic activity. The extents of isomeric site activity diminution were not proportional, resulting in alterations in the metabolite profiles. The results suggest that if a metabolite of CYP1B1 or elimination of a metabolite by CYP1B1 is necessary for normal embryonic or fetal tissue development, the appearance of these two mutations could result in developmental abnormalities. The altered activities of the mutants and ability of CYP1B1 to respond to external challenge may be the basis for the observed incomplete penetrance.

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药物酶

药物	酶	类	生物	药理作用	行动
孕酮	细胞色素P450 1 b1	蛋白质	人类	未知的	底物	细节