Abstract：
:The esterification of lysophospholipids contributes to phospholipid synthesis, remodeling, and scavenging. Acyl-CoA-dependent lysophospholipid acyltransferase activity with broad substrate use is mediated by Saccharomyces cerevisiae Lpt1p. We sought to identify Lpt1p active site amino acids besides the histidine conserved among homologs and repeatedly found to be required for catalysis. In vitro Lpt1p assays with amino acid modifying agents implicated aspartate, glutamate, and lysine as active site residues. Threonine and tyrosine were not ruled out. Aligning the primary structures of functionally characterized LPT1 homologs from fungi, plants, and animals identified 11 conserved aspartate, glutamate, lysine, threonine, and tyrosine residues. Site-directed mutagenesis of the respective codons showed that changing D146 and E297 abolished activity without abolishing protein expression. The mechanism of Lpt1p was further analyzed using monounsaturated acyl-CoA species with different double bond positions. Delta 6 species showed the highest catalytic efficiency. We propose that D146 and E297 act in conjunction with H382 as nucleophiles that attack the hydroxyl group in lysophospholipids in a general acid/base mechanism. This sequential mechanism provides a precedent for other members of the membrane bound O-acyltransferase family. Also, Lpt1p optimally orients acyl-CoA substrates with 7.5 Å between a double bond and the thioester bond.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Renauer P,Nasiri N,Oelkers Pdoi
10.1194/jlr.M062141subject
Has Abstractpub_date
2015-11-01 00:00:00pages
2143-50issue
11eissn
0022-2275issn
1539-7262pii
jlr.M062141journal_volume
56pub_type
杂志文章abstract：:Liver microsomal lipid peroxidation has been observed in fatal human CCl(4) poisoning, in rats with fatty livers induced by CCl(4) or by yellow phosphorus, and in mice poisoned with 1,1,2,2-tetrachloroethane. These observations suggest the possibility that other instances of toxic liver injury may involve lipid peroxi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-11-01 00:00:00
abstract：:Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25-50 mug/ml inhibited staurosporine-induced apoptosis in THP-1 cells...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700100-JLR200
更新日期：2008-01-01 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：:HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300091-JLR200
更新日期：2003-08-01 00:00:00
abstract：:The early premalignant liver provides a model in which to study metabolic alterations that may be permissive for the development of full malignancy. Although there are biochemical changes in this model, there are no detectable morphological ones when compared with a normal, fully differentiated liver. The maintenance ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Cellular membranes are composed of numerous kinds of glycerophospholipids with different combinations of polar heads at the sn-3 position and acyl moieties at the sn-1 and sn-2 positions, respectively. The glycerophospholipid compositions of different cell types, organelles, and inner/outer plasma membrane leaflets ar...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R046094
更新日期：2014-05-01 00:00:00
abstract：:Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-d-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain ar...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700406-JLR200
更新日期：2008-01-01 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 three-step procedure has been developed for the separation of complex mixtures of sterol intermediates in cholesterol biosynthesis. The method has been applied to the separation of sterol intermediates formed from [14C]mevalonate by normal rat hepatocyte culture cells. In Step 1, a short gravity-flow silicic acid co...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:In addition to its role in the uptake of apolipoprotein B (apoB)-containing lipoproteins, apoE promotes hepatic very low density lipoprotein-triglyceride (VLDL-TG) production in animal models. However, it is not known if apoE increases the amount of TG per VLDL particle or the number of VLDL particles secreted. VLDL-a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:Sequence homology indicates the existence of three human cytosolic acyl protein thioesterases, including APT1 that is known to depalmitoylate H- and N-Ras. One of them is the lysophospholipase-like 1 (LYPLAL1) protein that on the one hand is predicted to be closely related to APT1 but on the other hand might also func...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019851
更新日期：2012-01-01 00:00:00
abstract：:Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064709
更新日期：2016-07-01 00:00:00
abstract：:To assess the relationship between cholesterol synthesis and feedback inhibition of bile acid synthesis, we studied seven normal human subjects taking three different doses of chenodiol, 0, 5, and 15 mg/kg per day: once while taking no lovastatin and again while taking lovastatin 80 mg/day. Lovastatin and both doses o...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1994-08-01 00:00:00
abstract：:The combination of daunorubicin (dnr) and cytarabine (Ara-C) is a cornerstone of treatment for acute myelogenous leukemia (AML); resistance to these drugs is a major cause of treatment failure. Ceramide, a sphingolipid (SL), plays a critical role in cancer cell apoptosis in response to chemotherapy. Here, we investiga...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000251
更新日期：2019-09-01 00:00:00
abstract：:The addition of a trans isomer of arachidonic acid (20:4 delta 14trans) to rat platelet suspensions inhibited the aggregation induced by 7.5 microM of arachidonic acid. This inhibitory effect of 20:4 delta 14trans was significant at concentrations of 7.5-22.5 microM and the range of inhibition was 20% at an inhibitor/...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Cellular cholesterol is known to be under homeostatic control in nonsteroidogenic cells, and this intrigued us to understand how such control works in steroidogenic cells that additionally use cholesterol for steroid hormone synthesis. We employed primary culture of rat ovarian granulosa cells to study how steroidogen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M030239
更新日期：2013-02-01 00:00:00
abstract：:Mitochondrial cholesterol is maintained within a narrow range to regulate steroid and oxysterol synthesis and to ensure mitochondrial function. Mitochondria acquire cholesterol through several pathways from different cellular pools. Here we have characterized mitochondrial import of endosomal cholesterol using Chinese...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M029942
更新日期：2012-12-01 00:00:00
abstract：:An in vitro method is presented which measures valid, unidirectional uptake rates for lipids across the intestinal brush border. This method combines analysis by a newly devised, double isotope counting system for solubilized tissue with the use of a nonabsorbable marker to correct gross uptake determinations for cont...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-03-01 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：:The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300453-JLR200
更新日期：2004-04-01 00:00:00
abstract：:Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2-/- mice contain reduced content of LDs and accumulate less ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M079764
更新日期：2017-11-01 00:00:00
abstract：:Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). The strikingly more severe course of WD is caused by genetic defects of LAL that leave no residual enzymatic activity. Mutations a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 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：:The conditions for the preparation of laurylsarcosyltaurine from lauric acid and sarcosyltaurine, a crystalline dipeptide, are described. The preparation of sarcosyltaurine from the reaction of taurine and the mixed anhydride of benzyloxycarbonylsarcosine and isobutyl chloroformate is also described. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-03-01 00:00:00
abstract：:Cigarette smokers have reduced levels of plasma high density lipoprotein (HDL) compared to nonsmokers and are at risk of premature cardiovascular disease. Previous work from this laboratory has shown that exposure of human plasma to gas-phase cigarette smoke (CS) inhibited the activity of lecithin:cholesterol acyltran...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:Genetic polymorphisms of apolipoprotein A-IV (apoA-IV) have been detected by isoelectric focusing of serum proteins. Because genetic variation in apoA-IV has significant effects on lipid risk factors, we used restriction enzyme isoform genotyping (restriction isotyping) to determine apoA-IV isoform genotypes at the DN...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:A gas-liquid chromatography-flame ionization detection method is described for measuring plasma levels of eicosatetraynoic acid using eicosatriynoic acid as an internal standard. The technique is simple, rapid, and reproducible. Eicosatetraynoic acid and eicosatriynoic acid behave similarly in the extraction system ch...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. Mice received oleic acid (control group), EPA and DHA ethyl esters starting 10 days before tumor inoculation. Anal...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
