Abstract：
:In mammals, the esterification of sterols by ACAT plays a critical role in eukaryotic lipid homeostasis. Using the predominant isoform of the yeast ACAT-related enzyme family, Are2p, as a model, we targeted phylogenetically conserved sequences for mutagenesis in order to identify functionally important motifs. Deletion, truncation, and missense mutations implicate a regulatory role for the amino-terminal domain of Are2p and identified two carboxyl-terminal motifs as required for catalytic activity. A serine-to-leucine mutation in the (H/Y)SF motif (residues 338-340), unique to sterol esterification enzymes, nullified the activity and stability of yeast Are2p. Similarly, a tyrosine-to-alanine change in the FYxDWWN motif of Are2p (residues 523-529) produced an enzyme with decreased activity and apparent affinity for oleoyl-CoA. Mutagenesis of the tryptophan residues in this motif completely abolished activity. In human ACAT1, mutagenesis of the corresponding motifs (residues 268-270, and 403-409, respectively) also nullified enzymatic activity. On the basis of their critical roles in enzymatic activity and their sequence conservation, we propose that these motifs mediate sterol and acyl-CoA binding by this class of enzymes.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Guo Z,Cromley D,Billheimer JT,Sturley SLkeywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
1282-91issue
8eissn
0022-2275issn
1539-7262journal_volume
42pub_type
杂志文章abstract：:The isolated perfused mouse liver was utilized to evaluate the relative contribution of various molecules believed to participate in the removal of chylomicron remnants by the liver. Sixty percent of asialofetuin was removed from the perfusate per pass; bovine serum albumin was not removed. Normal mouse livers removed...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:We investigated the role of caveolae in uptake and intracellular trafficking of long chain fatty acids (LCFA) in HepG2 human hepatoma cells. The uptake of [(3)H]oleic acid and [(3)H]stearic acid into HepG2 cells was measured by radioactive assays and internalization of the non-metabolizable fluorescent fatty acid 12-(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100404-jlr200
更新日期：2002-09-01 00:00:00
abstract：:SREBP-2 activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in the intestine, we generated a mouse model (Vil-BP2-/- ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2-/- mice had reduced expression of genes required for sterol synt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M077610
更新日期：2017-10-01 00:00:00
abstract：:A facile procedure is described for the preparation of [14C]epicholesterol from [14C]cholesterol. Cholesterol is first converted to cholesteryl mesylate, which is treated with cesium acetate and 18-crown-6 in refluxing toluene to give epicholesteryl acetate. The latter is hydrolyzed, without isolation, with potassium ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Hyperlipidemia and marrow fat are associated with lowering bone density in vivo, suggesting that lipid contributes to bone loss. Using bone marrow-derived macrophages, we investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was signifi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800626
更新日期：2010-05-01 00:00:00
abstract：:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. More than half of older AML patients fail to respond to cytotoxic chemotherapy, and most responders relapse with drug-resistant disease. Failure to achieve complete remission can be partly attributed to the drug resistance advantage of AML blast...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M091876
更新日期：2019-06-01 00:00:00
abstract：:Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and en...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R900010-JLR200
更新日期：2009-10-01 00:00:00
abstract：:Liver and kidney microsomes have been found to catalyze a rapid decarboxylation of retinoic acid in vitro. The reaction requires NADPH and Fe(2+), and is further stimulated by the presence of pyrophosphate. Thiamine pyrophosphate contained sufficient iron as an impurity to provide strong enhancement of the reaction in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-07-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-03 00:00:00
abstract：:Major neutral glycosphingolipid components were extracted from Sporothrix schenckii, a dimorphic fungus exhibiting a hyphal saprophytic phase and a yeast parasitic phase responsible for chronic mycotic infections in mammalian hosts. These components, one from the mycelial form and two from the yeast form, were purifie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:The formation of cholic acid from 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA) was studied in two normal subjects. [3H]THCA and [14C]cholic acid were administered intravenously by simultaneous injection and the specific activities (percent injected amount/mumol) of [3H]- and [14C]cholic acid w...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-09-01 00:00:00
abstract：:Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation that acts primarily via a seven-transmembrane-spanning, G-protein-coupled receptor denoted BLT1. Here, we describe the synthesis and characterization of fluorescent analogs of LTB4 that are easy to produce, inexpensive, and without the disadvantages of a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500005-JLR200
更新日期：2005-06-01 00:00:00
abstract：:Macrophages contain a neutral cholesteryl ester hydrolase that can be activated by cAMP-dependent protein kinase. Immunological studies strongly suggest that hormone-sensitive lipase (HSL) is probably responsible for the cholesteryl ester hydrolase activity in macrophages; however, due to the very low level of express...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:Scavenger receptor class B type I (SR-BI) and ABCA1 are structurally dissimilar cell surface proteins that play key roles in HDL metabolism. SR-BI is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterifi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300358-JLR200
更新日期：2004-07-01 00:00:00
abstract：:Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054882
更新日期：2015-07-01 00:00:00
abstract：:Structurally specific very low density lipoprotein (VLDL) particles are presumed to redirect VLDL uptake during yolk deposition. Egg production is an energy intensive process, but energy excess negatively affects egg production. This study sought to determine whether overfeeding changed hen lipoprotein profiles, and i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:Several studies have documented the presence of Lp[a] in nonhuman primates. However, data are lacking in great apes such as the chimpanzee. We have studied the quantitative distribution of Lp[a], as well as the frequency of apo[a] phenotypes, in a population of chimpanzees living in Gabon. Monoclonal antibody 14A12, d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Bovine aortic endothelial cells take up 12-hydroxyeicosatetraenoic acid (12-HETE), a lipoxygenase product formed from arachidonic acid. The uptake of [3H]12-HETE reached a maximum in 2 to 4 h. At this time, from 75 to 80% of the incorporated radioactivity was contained in phospholipids, about 85% of the esterified rad...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Rabbits were fed either 10% coconut oil, 10% coconut oil and 1% beta-sitosterol, 10% coconut oil and 1% cholesterol, or 10% coconut oil and 1% beta-sitosterol plus 1% cholesterol for 4 weeks. Microsomal membranes from intestines of animals fed the 1% beta-sitosterol diet had 48% less cholesterol and were enriched twof...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-04-01 00:00:00
abstract：:Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subject...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800200-JLR200
更新日期：2008-09-01 00:00:00
abstract：:In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M085191
更新日期：2018-12-01 00:00:00
abstract：:Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. Purified ACSL4 is an arachidonic acid (20:4)-preferring ACSL isoform, and ACSL4 is therefore a probable regulator of lipid mediator production in intact cells. Eicosanoids play important roles in ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M013292
更新日期：2011-04-01 00:00:00
abstract：:Lymph chylomicrons of different sizes are known to be cleared at different rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between small and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600136-JLR200
更新日期：2006-11-01 00:00:00
abstract：:Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endolysosomal sys...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000516
更新日期：2020-07-01 00:00:00
abstract：:The binding of monoacylglycerides of long-chain fatty acids to human serum albumin has been examined using monooleoylglycerol as the ligand. Binding was investigated using changes in tryptophan fluorescence and also the displacement of a variety of well-studied fluorescent ligands from human serum albumin (HSA). Monoo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-∆7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120001101
更新日期：2020-11-17 00:00:00
abstract：:Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and apolipoproteins predict vascular events in the general and type 2 diabetes populations, but data in T1D are limited. We examined associations of ADLS, serum apolipoproteins, and conventional lipids with carotid intima-media thickness (IMT) measured c...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P080143
更新日期：2018-05-01 00:00:00
abstract：:Animal experiments show that the kidney contributes to apolipoprotein (apo)A-I catabolism. We tested relationships of HDL cholesterol (HDL-C) and apo-I with kidney function in subjects without severe chronic kidney disease. Included was a random sample of the general population (part of the PREVEND cohort). Kidney fun...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M005348
更新日期：2010-07-01 00:00:00
abstract：:In the present study, we have examined the structure of human low density lipoprotein (LDL) using cryo-electron microscopy. Human LDL particles were analyzed in a vitrified frozen-hydrated condition, without chemical fixation or any form of staining. Hence, the lipoproteins were visualized close to their native state....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
