CHOLESTEROL BIOSYNTHESIS CONTROL IN LIVER AND INTESTINE

肝脏和肠道中的胆固醇生物合成控制

基本信息

批准号：
3334186
负责人：
ALLEN COOPER
金额：
$ 22.85万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-05-01 至 1986-06-30
项目状态：
已结题

项目摘要

Cholersterol esters are the storage form of cholesterol. The distribution between free and esterified cholesterol may be an important determinant of cholesterol homeostasis. The rate of cholesterol esterification is determined by the activity of the enzyme acyl CoA: cholesterol acyltransferase. We propose to study the mechanisms of regulation of this enzyme in detail. Initially in vitro studies will be utilized to elucidate the mechanism of the rapid response of this enzyme to steroids. To do this, techniques for addition to steroids to microsomes have been devised as has a method of kinetic analysis. The importance of membrane bulk phase lipid fluidity as well as sterol domains in the process will be assessed by electron spin resonance and possibly fluorescence polarization. These techniques will be extended to livers whose sterol content has been affected by physiologic stimuli. The importance of other reactants (acyl CoA and cholerterol esters) will also be studied as will the possibilities that the enzyme is partially latent, can be activated by covalent modification and can be increased or decreased in quantity. Purification of the enzyme will be done to further study its regulation. The physiologic implications of alteration of this enzyme's activity are being studied in isolated liver and in intestine. Finally we propsed to conclude our studies on the characterization and regulation of intestinal HMG-CoA reductase.

胆固醇酯是胆固醇的储存形式。分布在自由和酯化胆固醇之间可能是胆固醇稳态。确定胆固醇酯化速率通过酶酰基COA的活性：胆固醇酰基转移酶。我们建议详细研究该酶调节的机制。最初体外研究将用于阐明快速反应的机制将这种酶与类固醇。为此，将类固醇添加到微粒体已被设计为动力学分析方法。这膜散装相脂质流动性以及固醇结构域的重要性该过程将通过电子自旋共振以及可能的荧光极化。这些技术将扩展到其固醇含量为受生理刺激的影响。其他反应物（酰基COA）的重要性也将研究胆固醇酯）。酶是部分潜在的，可以通过共价修改激活，并且可以是数量增加或减少。酶的纯化将进行进一步研究其调节。这种酶活性改变的生理含义正在在孤立的肝脏和肠中进行了研究。最后，我们支撑了有关特征和的研究调节肠HMG-COA还原酶。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rat liver acyl-coenzyme A:cholesterol acyltransferase: its regulation in vivo and some of its properties in vitro.

大鼠肝酰基辅酶 A：胆固醇酰基转移酶：其体内调节及其体外一些特性。

DOI：
发表时间：
1980
期刊：
Journal of lipid research
影响因子：
6.5
作者：
Erickson,SK;Shrewsbury,MA;Brooks,C;Meyer,DJ
通讯作者：
Meyer,DJ

Changes in parameters of lipoprotein metabolism during rat hepatic development.

大鼠肝脏发育过程中脂蛋白代谢参数的变化。

DOI：
10.1016/0005-2760(88)90321-9
发表时间：
1988
期刊：
Biochimica et biophysica acta
影响因子：
0
作者：
Erickson,SK;Bruscalupi,G;ContiDevirgiliis,L;Leoni,S;Mangiantini,MT;Spagnuolo,S;Trentalance,A
通讯作者：
Trentalance,A

Cholesterol 7 alpha-hydroxylase from human liver: partial purification and reconstruction into defined phospholipid-cholesterol vesicles.

来自人肝脏的胆固醇 7 α-羟化酶：部分纯化并重建为确定的磷脂-胆固醇囊泡。

DOI：
发表时间：
1981
期刊：
Journal of lipid research
影响因子：
6.5
作者：
Erickson,SK;Bösterling,B
通讯作者：
Bösterling,B

Changes in lipoprotein binding and uptake by hepatocytes during rat liver regeneration.

大鼠肝脏再生过程中脂蛋白结合和肝细胞摄取的变化。

DOI：
10.1007/bf01116000
发表时间：
1989
期刊：
Bioscience reports
影响因子：
4
作者：
Trentalance,A;Bruscalupi,G;ContiDevirgiliis,L;Leoni,S;Mangiantini,MT;Rossini,L;Spagnuolo,S;Erickson,SK
通讯作者：
Erickson,SK

Acyl-coenzyme A:cholesterol acyltransferase in human liver. In vitro detection and some characteristics of the enzyme.

酰基辅酶A：人肝脏中的胆固醇酰基转移酶。