Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages.

Abstract:

:Apicomplexan parasites are pathogens responsible for major human diseases such as toxoplasmosis caused by Toxoplasma gondii and malaria caused by Plasmodium spp. Throughout their intracellular division cycle, the parasites require vast and specific amounts of lipids to divide and survive. This demand for lipids relies on a fine balance between de novo synthesized lipids and scavenged lipids from the host. Acetyl-CoA is a major and central precursor for many metabolic pathways, especially for lipid biosynthesis. T. gondii possesses a single cytosolic acetyl-CoA synthetase (TgACS). Its role in the parasite lipid synthesis is unclear. Here, we generated an inducible TgACS KO parasite line and confirmed the cytosolic localization of the protein. We conducted 13C-stable isotope labeling combined with mass spectrometry-based lipidomic analyses to unravel its putative role in the parasite lipid synthesis pathway. We show that its disruption has a minor effect on the global FA composition due to the metabolic changes induced to compensate for its loss. However, we could demonstrate that TgACS is involved in providing acetyl-CoA for the essential fatty elongation pathway to generate FAs used for membrane biogenesis. This work provides novel metabolic insight to decipher the complex lipid synthesis in T. gondii.

journal_name

J Lipid Res

authors

Dubois D,Fernandes S,Amiar S,Dass S,Katris NJ,Botté CY,Yamaryo-Botté Y

doi

10.1194/jlr.M082891

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

994-1004

issue

6

eissn

0022-2275

issn

1539-7262

pii

jlr.M082891

journal_volume

59

pub_type

杂志文章
  • Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells.

    abstract::Niemann-Pick C1-like 1 (NPC1L1) is a recently identified protein that mediates intestinal cholesterol absorption and regulates biliary cholesterol excretion. The itineraries and kinetics of NPC1L1 trafficking remain uncertain. In this study, we have visualized movement of NPC1L1-enhanced green fluorescent protein (NPC...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800145-JLR200

    authors: Petersen NH,Faergeman NJ,Yu L,Wüstner D

    更新日期:2008-09-01 00:00:00

  • The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes.

    abstract::Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a group of rare genetic disorders of HDL metabolism that have been the subject of a large number of clinical, biochemical, and genetic studies. Of special interest are patients with LCAT-related disorders with severe HDL deficiency and the appa...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:

    authors: Kuivenhoven JA,Pritchard H,Hill J,Frohlich J,Assmann G,Kastelein J

    更新日期:1997-02-01 00:00:00

  • Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells.

    abstract::Within the cholesterol biosynthesis cascade, the enzyme 2,3-oxidosqualene cyclase [EC 5.4.99.7] is of special interest due to its dual function: cyclization of 2,3-monoepoxysqualene to lanosterol and 2,3;22,23-diepoxysqualene to oxylanosterol. Further determination of the significance of this enzyme for the intracellu...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Mark M,Muller P,Maier R,Eisele B

    更新日期:1996-01-01 00:00:00

  • Recovery and activation of hydroxymethylglutaryl coenzyme A reductase from rat small intestine.

    abstract::We describe a method for estimating the total activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) in the small intestine of rats. An homogenate of the whole small intestine is prepared rapidly and assayed directly to maximize the yield of enzyme and to minimize opportunity for uncontrolled cha...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Young NL,Saudek CD,Crawford SA,Zuckerbrod SL

    更新日期:1982-02-01 00:00:00

  • SREBP1 is required for the induction by glucose of pancreatic beta-cell genes involved in glucose sensing.

    abstract::Previous studies have reported both positive and negative effects of culture of islets at high glucose concentrations on regulated insulin secretion. Here, we have reexamined this question in mouse islets and determined the role of changes in lipid synthesis in the effects of glucose. Glucose-stimulated insulin secret...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M700533-JLR200

    authors: Diraison F,Ravier MA,Richards SK,Smith RM,Shimano H,Rutter GA

    更新日期:2008-04-01 00:00:00

  • Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography.

    abstract::We examined the association between rate of cholesterol esterification in plasma depleted of apolipoprotein B-containing lipoproteins (FER(HDL)), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclero...

    journal_title:Journal of lipid research

    pub_type: 临床试验,杂志文章

    doi:10.1194/jlr.P011668

    authors: Dobiásová M,Frohlich J,Sedová M,Cheung MC,Brown BG

    更新日期:2011-03-01 00:00:00

  • Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T schwannoma cells.

    abstract::Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly exp...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800666-JLR200

    authors: Alderson NL,Hama H

    更新日期:2009-06-01 00:00:00

  • ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study.

    abstract::The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein levels, and allele frequencies differ between African Americans and Caucasians. As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians, we investigated the effects of the apoE gene on allele-specific apolipoprotei...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M600431-JLR200

    authors: Anuurad E,Lu G,Rubin J,Pearson TA,Berglund L

    更新日期:2007-03-01 00:00:00

  • Hypervariability in a minisatellite 3' of the apolipoprotein B gene in patients with coronary heart disease compared with normal controls.

    abstract::Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Friedl W,Ludwig EH,Paulweber B,Sandhofer F,McCarthy BJ

    更新日期:1990-04-01 00:00:00

  • Biliary lipid secretion in hypercholesterolemia.

    abstract::A report on the effects of primary bile acid ingestion alone or in combination with plant sterols on serum cholesterol levels, biliary lipid secretion, and bile acid metabolism. Biliary bile acid and cholesterol secretion were measured in four patients with type IIa hypercholesterolemia before and after randomized tre...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Tangedahl TN,Hofmann AF,Kottke BA

    更新日期:1979-01-01 00:00:00

  • Effects of cholesterol in chylomicron remnant models of lipid emulsions on apoE-mediated uptake and cytotoxicity of macrophages.

    abstract::Chylomicron remnants have been suggested to be involved in the development of atherosclerosis. To investigate the mechanisms of chylomicron remnant-induced atherosclerosis, we prepared cholesterol (Chol)-containing emulsion particles as models for chylomicron remnants. Chol markedly increased the apolipoprotein E (apo...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M500167-JLR200

    authors: Sakurai A,Morita SY,Wakita K,Deharu Y,Nakano M,Handa T

    更新日期:2005-10-01 00:00:00

  • Aliphatic medium chain tricarboxylic acids in rat urine.

    abstract::Three aliphatic tricarboxylic acids have been found in rat urine. They have been identified as 6-carboxy-5-undecenedioic acid, 6-carboxy-5-dodecenedoic acid, and 6-carboxy-5-tridecenedioic acid. The carbon skeleton structure was determined by mass spectra of the hydrogenated methyl esters. The double bond position was...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Eliasson B,Lindstedt S,Steen G

    更新日期:1976-11-01 00:00:00

  • Lipidome-wide 13C flux analysis: a novel tool to estimate the turnover of lipids in organisms and cultures.

    abstract::Lipid metabolism plays an important role in the regulation of cellular homeostasis. However, because it is difficult to measure the actual rates of synthesis and degradation of individual lipid species, lipid compositions are often used as a surrogate to evaluate lipid metabolism even though they provide only static s...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.D119000318

    authors: Schlame M,Xu Y,Erdjument-Bromage H,Neubert TA,Ren M

    更新日期:2020-01-01 00:00:00

  • Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid.

    abstract::The resistin gene is expressed in adipocytes and encodes a protein proposed to link obesity and type 2 diabetes. Increased plasma FFA is associated with insulin resistance. We examined the effect of separate FFAs on the expression of resistin mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M400348-JLR200

    authors: Haugen F,Zahid N,Dalen KT,Hollung K,Nebb HI,Drevon CA

    更新日期:2005-01-01 00:00:00

  • Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation.

    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

    authors: Tan SF,Dunton W,Liu X,Fox TE,Morad SAF,Desai D,Doi K,Conaway MR,Amin S,Claxton DF,Wang HG,Kester M,Cabot MC,Feith DJ,Loughran TP Jr

    更新日期:2019-06-01 00:00:00

  • Modified spray for the detection of phospholipids on thin-layer chromatograms.

    abstract::A simplified method for the preparation of the Dittmer-Lester spray for the detection of phospholipids on thin-layer chromatograms is described. ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Vaskovsky VE,Kostetsky EY

    更新日期:1968-05-01 00:00:00

  • Quantitation of model digestive mixtures by 13C NMR.

    abstract::13C nuclear magnetic resonance (NMR) spectra were obtained at 50.3 and 100.5 MHz for methanolic and aqueous mixtures of sodium taurocholate, 1-monocapryloyl-rac-glycerol, and caprylic acid. Distortionless Enhancement by Polarization Transfer (DEPT) was used to improve spectral sensitivity and resolution, and to genera...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Wang D,Hadipour NL,Jerlin EA,Stark RE

    更新日期:1992-03-01 00:00:00

  • Characterization and synthesis of mono- and diphytanyl ethers of glycerol.

    abstract::The methanolyzed lipids of the extreme halophile, Halobacterium cutirubrum, were separated into glycerol diether and glycerol monoether fractions. The diether was shown by synthesis to be 2,3-di-O-(3'R,7'R,11'R,15'-tetramethylhexadecyl)-sn-glycerol. The monoether fraction was separated by thin-layer chromatography on ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Joo CN,Shier T,Kates M

    更新日期:1968-11-01 00:00:00

  • Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112.

    abstract::Human apolipoprotein (apo) E occurs as three common isoforms (apoE4, E3, and E2), all of which influence plasma cholesterol levels. Although both apoE4 and E3 bind with equal effectiveness to the low density lipoprotein receptor, they associate preferentially with different classes of plasma lipoproteins: apoE4 with v...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Weisgraber KH

    更新日期:1990-08-01 00:00:00

  • Plasma lipoproteins in the golden Syrian hamster (Mesocricetus auratus): heterogeneity of apoB- and apoA-I-containing particles.

    abstract::We present the quantitative and qualitative characteristics of the apolipoprotein (apo) B- and apoA-I-containing lipoprotein subspecies in the plasma of male Golden Syrian hamsters. The spectrum of hamster lipoproteins of d < 1.172 g/ml was subfractionated by isopycnic density gradient ultracentrifugation. ApoB-contai...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Goulinet S,Chapman MJ

    更新日期:1993-06-01 00:00:00

  • Studies on the metabolic fate of n-3 polyunsaturated fatty acids.

    abstract::Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14C] 24:6n-3 was 2.7 times higher than for [1-14C]22:6n-3, whereas [1-14C]22:6n-3 was incorporat...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M300223-JLR200

    authors: Ferdinandusse S,Denis S,Dacremont G,Wanders RJ

    更新日期:2003-10-01 00:00:00

  • Apolipoprotein H: a two-step isolation method.

    abstract::A new method for the purification of apolipoprotein H by affinity chromatography followed by continuous-elution electrophoresis is described. It is both simpler and less complicated than the chromatographic and electrophoretic methods usually used. In addition, apolipoprotein H is isolated in a pure, structurally uncl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Gambino R,Ruiu G,Cassader M,Pagano G

    更新日期:1996-04-01 00:00:00

  • Using bioinformatics and systems genetics to dissect HDL-cholesterol genetics in an MRL/MpJ x SM/J intercross.

    abstract::A higher incidence of coronary artery disease is associated with a lower level of HDL-cholesterol. We searched for genetic loci influencing HDL-cholesterol in F2 mice from a cross between MRL/MpJ and SM/J mice. Quantitative trait loci (QTL) mapping revealed one significant HDL QTL (Apoa2 locus), four suggestive QTL on...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M025833

    authors: Leduc MS,Blair RH,Verdugo RA,Tsaih SW,Walsh K,Churchill GA,Paigen B

    更新日期:2012-06-01 00:00:00

  • Retroperitoneal white adipose tissue lipoprotein lipase activity is rapidly down-regulated in response to acute stress.

    abstract::Tissue-specific regulation of LPL has been widely studied in rats. Previous studies reported that in vivo administration of adrenaline and acute stress cause an increase in plasma LPL activity coinciding with a decrease in white adipose tissue (WAT) LPL activity. We studied the speed of LPL activity changes during 30 ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M600487-JLR200

    authors: Casanovas A,Parramon N,de la Cruz F,Andrés O,Terencio J,López-Tejero MD,Llobera M

    更新日期:2007-04-01 00:00:00

  • Scap is required for sterol synthesis and crypt growth in intestinal mucosa.

    abstract::SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synt...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M059709

    authors: McFarlane MR,Cantoria MJ,Linden AG,January BA,Liang G,Engelking LJ

    更新日期:2015-08-01 00:00:00

  • Rapid determination of apolipoprotein E genotype using a heteroduplex generator.

    abstract::The apoE gene exhibits two common polymorphisms that have been associated with both coronary artery disease and Alzheimer's disease. The polymorphisms create the three allelic isoforms E2, E3, and E4 which are encoded by Cys;-Cys, Cys;-Arg, and Arg;-Arg at amino acid positions 112 and 158, respectively. Numerous metho...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Bolla MK,Wood N,Humphries SE

    更新日期:1999-12-01 00:00:00

  • The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion.

    abstract::In order to study the metabolic responses of humans consuming a diet moderately high in cholesterol content, we carried out a long-term sterol balance study, up to 25 weeks in duration. Two subjects, one normocholesterolemic and one hypercholesterolemic, were given, in sequence, a very low cholesterol diet and then a ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Lin DS,Connor WE

    更新日期:1980-11-01 00:00:00

  • Dimorphic expression of cerebrosides in the mycopathogen Sporothrix schenckii.

    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:

    authors: Toledo MS,Levery SB,Straus AH,Takahashi HK

    更新日期:2000-05-01 00:00:00

  • Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    abstract::apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipos...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M050567

    authors: Huang ZH,Reardon CA,Getz GS,Maeda N,Mazzone T

    更新日期:2015-02-01 00:00:00

  • Structural analysis of novel bioactive acylated steryl glucosides in pre-germinated brown rice bran.

    abstract::Previous studies from our laboratory indicated that pre-germinated brown rice (PR) contained certain unknown bioactive lipids that activated two enzymes related to diabetes: Na+/K+ATPase and homocysteine-thiolactonase. In this paper, we report on the isolation and structural characterization of the activator lipids fr...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800257-JLR200

    authors: Usuki S,Ariga T,Dasgupta S,Kasama T,Morikawa K,Nonaka S,Okuhara Y,Kise M,Yu RK

    更新日期:2008-10-01 00:00:00