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Characterization of novel human UDP glycosyltransferases

新型人 UDP 糖基转移酶的表征

基本信息

批准号：
nhmrc : 275544
负责人：
E/Pr Peter Mackenzie
金额：
$ 27.86万
依托单位：
Flinders University
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2004
资助国家：
澳大利亚
起止时间：
2004-01-01 至 2006-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/characterization-novel-human-udp-glycosyltransferases/96758
关键词：
Characterization novel human UDP glycosyltransferases

项目摘要

Our defense against the toxic effects of small organic molecules is mediated by families of enzymes found in the internal membranes of cells, predominantly in the liver and gastrointestinal tract. Many small organic molecules, such as environmental pollutants, carcinogens and therapeutic drugs, are fat-soluble and will accumulate in the body to toxic levels unless they are modified by the addition of water-soluble groups. The modified chemical, in the majority of cases, is less toxic and readily removed from the body. One aim of this project is to identify and characterize newly discovered enzymes in the family that uses sugar residues to modify and eliminate fat-soluble chemicals. Their involvement in the detoxification process and how they are controlled in the cell will be determined. These are the final enzymes in this family remaining to be characterized in humans. In addition to foreign chemicals and toxins, this enzyme family also regulates the intracellular concentrations of signalling molecules such as steroid hormones and chemicals that bind to gene regulatory proteins. Defects and-or variations in these enzymes may alter the levels of these signalling molecules and lead to uncontrolled cell growth (cancer) or cell death. A second aim of this project is to determine whether these novel enzymes are involved in controlling signal concentrations and to determine whether inherited variations in these enzymes will alter the signalling process.

我们对小有机分子毒性作用的防御是由细胞内膜中发现的酶家族介导的，主要是在肝脏和胃肠道中。许多小的有机分子，如环境污染物、致癌物和治疗药物，是脂溶性的，除非通过添加水溶性基团对其进行修饰，否则将在体内积累至毒性水平。在大多数情况下，改性化学品毒性较小，易于从体内清除。该项目的一个目的是确定和表征新发现的酶家族，该家族使用糖残基来修饰和消除脂溶性化学物质。它们参与解毒过程以及它们在细胞中如何被控制将被确定。这些是该家族中最后一种有待在人类中表征的酶。除了外源化学物质和毒素外，该酶家族还调节信号分子的细胞内浓度，如类固醇激素和与基因调节蛋白结合的化学物质。这些酶的缺陷和/或变异可能会改变这些信号分子的水平，导致细胞生长失控（癌症）或细胞死亡。该项目的第二个目的是确定这些新的酶是否参与控制信号浓度，并确定这些酶的遗传变异是否会改变信号传导过程。