Ontogeny of acyl-CoA: cholesterol acyltransferase in rat liver, intestine, and adipose tissue

1992 ◽  
Vol 262 (4) ◽  
pp. G599-G602
Author(s):  
M. T. Little ◽  
P. Hahn
Keyword(s):  
Adipose Tissue ◽  
Rat Liver ◽  
Animal Studies ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Cholesterol Acyltransferase ◽  
Dietary Manipulation ◽  
Acat Activity ◽  
Brown Adipose ◽  
Acyl Coenzyme A

The development of acyl-coenzyme A: cholesterol acyltransferase (ACAT), was determined in the rat liver, intestine, and white (WAT) and brown adipose tissue (BAT). Animal studies have shown that dietary manipulation of cholesterol metabolism during an animal's early development can have persistent and permanent effects. Therefore it is important that the ontogeny of ACAT, one of the key enzymes in cholesterol metabolism, be clearly established. White Wistar rats were killed on day 21 of gestation, at birth, and on postnatal days 10, 14, 18, 21, 22, 25, 30, and 60. The tissues were rapidly excised, microsomes were prepared, and the activity of ACAT was measured as the rate of incorporation of [1-14C]oleoyl coenzyme A into cholesterol esters. Age-specific changes were observed in three of the four tissues investigated. Rat liver and intestine possess significant amounts of ACAT activity throughout development with marked variations in activity during this time. ACAT activity in BAT is low and variable throughout development with the exception of high activity noted in the adult animal. WAT contained little or no ACAT activity during development.

Acyl-Coenzyme A—Cholesterol Acyltransferase Activity in Human Liver

1979 ◽  
Vol 56 (4) ◽  
pp. 373-375 ◽  
Author(s):  
S. Balasubramaniam ◽  
K. A. Mitropoulos ◽  
N. B. Myant ◽  
M. Mancini ◽  
A. Postiglione
Keyword(s):  
Liver Enzyme ◽  
Rat Liver ◽  
Human Liver ◽  
Microsomal Fraction ◽  
Coenzyme A ◽  
Cholesterol Acyltransferase ◽  
Liver Microsomes ◽  
Cholesteryl Oleate ◽  
Acyltransferase Activity ◽  
Acyl Coenzyme A

1. In the presence of CoA and ATP, human liver microsomes catalyse the incorporation of [14C]oleate or [14C]cholesterol into cholesteryl oleate, thus demonstrating the presence of acyl-coenzyme A-cholesterol acyltransferase (cholesterol acyltransferase) in human liver. 2. The enzyme has properties similar to those of rat liver enzyme and with both the concentration of endogenous cholesterol in the microsomal fraction is adequate to support a constant initial rate of esterification. However, unlike the rat liver enzyme, the human cholesterol acyltransferase does not efficiently utilize added cholesterol as substrate. 3. The activity of cholesterol acyltransferase in human liver was 25% of that measured in rat liver under similar conditions of assay.

Androgen-mediated cholesterol metabolism in LNCaP and PC-3 cell lines is regulated through two different isoforms of acyl-coenzyme A: Cholesterol Acyltransferase (ACAT)

The Prostate ◽  
2007 ◽  
Vol 68 (1) ◽  
pp. 20-33 ◽  
Author(s):  
Jennifer A. Locke ◽  
Kishor M. Wasan ◽  
Colleen C. Nelson ◽  
Emma S. Guns ◽  
Carlos G. Leon
Keyword(s):  
Cell Lines ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Cholesterol Acyltransferase ◽  
Acyl Coenzyme A

scholarly journals The effects of low-density lipoprotein and cholesterol on acyl-coenzyme A: cholesterol acyltransferase activity in membranes from cultured human fibroblasts

1983 ◽  
Vol 216 (1) ◽  
pp. 93-100 ◽  
Author(s):  
S J P Gavigan ◽  
B L Knight
Keyword(s):  
Coenzyme A ◽  
Low Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Low Density ◽  
Intact Cells ◽  
Cultured Fibroblasts ◽  
Normal Medium ◽  
Acat Activity ◽  
Acyl Coenzyme A

Membranes prepared from cultured fibroblasts were assayed for acyl-coenzyme A: cholesterol acyltransferase (ACAT) by a method that relied exclusively on the cholesterol already present on the membranes as the sterol substrate. Changes in membrane ACAT activity during incubation of fibroblasts under a variety of conditions were similar to the changes in the rate of incorporation of oleic acid into cholesteryl esters by the intact cells. The addition of low-density lipoprotein (LDL) to fibroblasts pre-incubated with lipoprotein-deficient serum led to a transient increase in membrane ACAT activity, which reached its peak after 7h and was related to the receptor-mediated uptake and degradation of the lipoprotein by the cells. However, after incubation of the membranes with a cholesterol-rich donor lipoprotein, which resulted in an equilibration of cholesterol between membranes and donor, each preparation exhibited the same activity. In contrast with these effects of LDL, incubation of the cells with non-esterified cholesterol produced a prolonged increase in ACAT activity and an increase in the activity observed after equilibration. Furthermore, ACAT activity in cells grown with linoleic acid was higher, both before and after the addition of LDL, than that of cells grown in normal medium or with palmitate. The increase in activity produced by LDL was also greater, reflecting the greater rate of degradation of LDL by the cells, and was associated with an increase in the activity observed after equilibration with donor. The results suggest that although fibroblasts can increase the amount of active enzyme on their membranes to accommodate an exceptionally high or prolonged supply of cholesterol, under normal circumstances the increase in membrane ACAT activity produced by LDL can be explained entirely by an increase in the amount of cholesterol in the substrate pool.

scholarly journals Acyl-Coenzyme A: Cholesterol Acyltransferase (ACAT) in Cholesterol Metabolism: From Its Discovery to Clinical Trials and the Genomics Era

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 543
Author(s):  
Qimin Hai ◽  
Jonathan D. Smith
Keyword(s):  
Clinical Trials ◽  
Cell Biology ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Association Studies ◽  
Cholesterol Acyltransferase ◽  
Lipid Absorption ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Acyl Coenzyme A

The purification and cloning of the acyl-coenzyme A: cholesterol acyltransferase (ACAT) enzymes and the sterol O-acyltransferase (SOAT) genes has opened new areas of interest in cholesterol metabolism given their profound effects on foam cell biology and intestinal lipid absorption. The generation of mouse models deficient in Soat1 or Soat2 confirmed the importance of their gene products on cholesterol esterification and lipoprotein physiology. Although these studies supported clinical trials which used non-selective ACAT inhibitors, these trials did not report benefits, and one showed an increased risk. Early genetic studies have implicated common variants in both genes with human traits, including lipoprotein levels, coronary artery disease, and Alzheimer’s disease; however, modern genome-wide association studies have not replicated these associations. In contrast, the common SOAT1 variants are most reproducibly associated with testosterone levels.

scholarly journals A Guanosine Triphosphate-dependent Acyl Coenzyme A Synthetase from Rat Liver Mitochondria

1967 ◽  
Vol 242 (9) ◽  
pp. 2111-2115 ◽  
Author(s):  
Lauro Galzigna ◽  
Carlo R. Rossi ◽  
Lodovico Sartorelli ◽  
David M. Gibson
Keyword(s):  
Rat Liver ◽  
Coenzyme A ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Guanosine Triphosphate ◽  
Acyl Coenzyme A

scholarly journals Oxidative phosphorylation. The specific binding of trimethyltin and triethyltin to rat liver mitochondria

1970 ◽  
Vol 118 (1) ◽  
pp. 171-179 ◽  
Author(s):  
W. N. Aldridge ◽  
B. W. Street
Keyword(s):  
Adipose Tissue ◽  
Oxidative Phosphorylation ◽  
Brown Adipose Tissue ◽  
Binding Site ◽  
Rat Liver ◽  
Specific Binding ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Affinity Constants ◽  
Brown Adipose

1. The binding of trimethyltin and triethyltin to rat liver mitochondria was determined and the results were analysed by the method of Scatchard (1949). 2. One binding site (site 1) has the correct characteristics for the site to which trimethyltin and triethyltin are attached when they inhibit oxidative phosphorylation. For each compound the concentration of site 1 is 0.8nmol/mg of protein and the ratios of their affinity constants are the same as the ratio of the concentrations inhibiting oxidative phosphorylation. 3. Binding site 1 is present in a fraction derived from mitochondria containing only 15% of the original protein. In this preparation ultrasonication rapidly destroyed site 1. 4. Dimethyltin and diethyltin do not prevent binding of triethyltin to rat liver mitochondria, whereas triethyl-lead does. 5. Trimethyltin and triethyltin bind to mitochondria from brown adipose tissue and the results indicate a binding site 1 similar to that in rat liver mitochondria. 6. The advantages and limitations of this approach to the study of inhibitors are discussed.

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