Functional analysis of long-chain acyl-CoA thioesterase gene expressed in the brain and testis.

大脑和睾丸中表达的长链酰基辅酶A硫酯酶基因的功能分析。

基本信息

批准号：
11672189
负责人：
YAMADA Junji
金额：
$ 1.98万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672189/
关键词：
acyl-CoA thioesterase long-chain acyl-CoA brain gene アシルコエンザイムA チオエステラーゼ精巣

项目摘要

Long-chain acyl-CoA thioesterases include a number of enzymes that catalyze the hydrolysis of fatty acyl-CoA thioesters to the corresponding free fatty acids and coenzyme A.It has been well documented that there is a markedly high level of hydrolytic activity toward long-chain acyl-CoAs in the brains of mammals, suggesting some specific role of the enzyme in this tissue. However, its physiological significance has remained unclear. In previous studies, we purified and characterized an enzyme, referred to as BACH (brain acyl-CoA hydrolase), from rat brain cytosol, and identified it as a novel long-chain acyl-CoA thioesterase by the cDNA cloning and sequence analysis. In rats, BACH was present at high levels both in the brain and testis, and accounted for the most part of palmitoyl-CoA hydrolyzing activities found there. In this study to gain an insight into physiological function of BACH, we investigated 1. Characteristics of human BACH and its gene structure ; 2. Mechanism of human BACH gene expression ; 3. Structural organization of mouse BACH gene ; 4. Tissue distribution of BACH in the mouse ; 5. Establishment of BACH gene-transfected cell lines ; and 6. Gene targeting. The findings obtained were very informative to understand biochemical and molecular biological properties of BACH, including catalytic and molecular properties, tissue and subcellular distribution, isoform formation, genomic organization, and transcriptional regulation. For further studies of BACH function, useful means were also provided. Thus, the present study will make a large contribution for a better understanding of physiological significance of BACH and probably this class of thioesterases.

长链酰基辅酶A硫酯酶包括许多酶，这些酶将脂肪酰基辅助硫硫代的水解催化为相应的游离脂肪酸和辅酶A.IT已经有充分的文献证明，它具有显着的水解水平高度高的哺乳动物的乳腺癌的水平，提出了一些特定的组织，这些角色提出了一些ENSZEME的作用。但是，其生理意义尚不清楚。在先前的研究中，我们从大鼠脑细胞质中纯化并表征了一种酶，称为BACH（脑酰基-COA水解酶），并通过cDNA克隆和序列分析将其鉴定为一种新型的长链链酰基辅助硫酯酶。在大鼠中，巴赫（Bach）在大脑和睾丸中都存在高水平，并且在那里发现了大部分棕榈酰-COA水解活动的大部分。在这项研究中，为了深入了解巴赫的生理功能，我们研究了1。人类巴赫的特征及其基因结构。 2。人Bach基因表达的机制； 3。小鼠bach基因的结构组织； 4。小鼠中巴赫的组织分布； 5。建立BACH基因转染的细胞系；和6。基因靶向。获得的发现非常有用，可以理解BACH的生化和分子生物学特性，包括催化和分子特性，组织和细胞亚分布，同工型形成，基因组组织以及转录调控。为了进一步研究BACH功能，还提供了有用的手段。因此，本研究将做出很大的贡献，以更好地理解BACH的生理意义以及这类硫代酶。