Abstract：
:Ethanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen [1-alkenyl-2-acyl-glycerophosphoethanolamine (plasmenyl-PE)]. However, to date there has been no analysis of the metabolomic consequences of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells. We studied a patient with severe complicated hereditary spastic paraplegia, sensorineural-deafness, blindness, and seizures. Neuroimaging revealed hypomyelination, followed by brain atrophy mainly in the cerebellum and brainstem. Using whole exome sequencing, we identified a novel EPT1 mutation (exon skipping). In vitro EPT activity, as well as the rate of biosynthesis of ethanolamine glycerophospholipids, was markedly reduced in cultures of the patient's skin fibroblasts. Quantification of phospholipids by LC-MS/MS demonstrated reduced levels of several PE species with polyunsaturated fatty acids, such as 38:6, 38:4, 40:6, 40:5, and 40:4. Notably, most plasmenyl-PE species were significantly decreased in the patient's cells, whereas most plasmanylcholine [1-alkyl-2-acyl-glycerophosphocholine (plasmanyl-PC)] species were increased. Similar findings regarding decreased plasmenyl-PE and increased plasmanyl-PC were obtained using EPT1-KO HeLa cells. Our data demonstrate for the first time the indispensable role of EPT1 in the myelination process and neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in humans.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Horibata Y,Elpeleg O,Eran A,Hirabayashi Y,Savitzki D,Tal G,Mandel H,Sugimoto Hdoi
10.1194/jlr.P081620subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1015-1026issue
6eissn
0022-2275issn
1539-7262pii
jlr.P081620journal_volume
59pub_type
杂志文章abstract：:The 3-methyl-branched fatty acid phytanic acid is degraded by the peroxisomal alpha-oxidation route because the 3-methyl group blocks beta-oxidation. In adult Refsum disease (ARD), peroxisomal alpha-oxidation is defective, which is caused by mutations in the gene coding for phytanoyl-CoA hydroxylase in the majority of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400064-JLR200
更新日期：2004-07-01 00:00:00
abstract：:A strategy has been developed for archaebacterial lipid analysis which provides three times the information to describe archaebacterial isolates and is compatible with simultaneous eubacterial/eukaryotic lipid analysis of environmental samples. Eubacterial and micro-eukaryotic biomass, community structure, and nutriti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:In mammals, white adipose tissue (WAT) stores and releases lipids, whereas brown adipose tissue (BAT) oxidizes lipids to fuel thermogenesis. In obese individuals, WAT undergoes profound changes; it expands, becomes dysfunctional, and develops a low-grade inflammatory state. Importantly, BAT content and activity declin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M079665
更新日期：2018-05-01 00:00:00
abstract：:Autosomal recessive polycystic kidney disease (ARPKD) is a severe, monogenetically inherited kidney and liver disease. PCK rats carrying the orthologous mutant gene serve as a model of human disease, and alterations in lipid profiles in PCK rats suggest that defined subsets of lipids may be useful as molecular disease...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M040014
更新日期：2013-10-01 00:00:00
abstract：:A two-step polymerase chain reaction (PCR) method for the rapid detection of the apolipoprotein B(Arg3500----Gln) mutation in a mixture of pooled blood samples is described. In the first step PCR, a short gene fragment surrounding codon 3500 is amplified. Subsequently the reaction product is subjected to a second ampl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：:Type 1 diabetes mellitus is a devastating disorder affecting both glucose and lipid metabolism. Using the nonobese diabetic (NOD) mouse model, we found that diabetic mice had a liver-specific increase in steady state mRNA levels for enzymes involved in oxidation of fatty acids. Increased mRNA abundance was observed in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:Adipose tissue development was studied histochemically and histologically in fetuses from lean and obese sows. At 110 days of gestation, fetuses were removed from Ossabaw (obese-feral) sows and from sows selected for high backfat (obese-domestic) and for low backfat (lean) thickness. Body weights were similar for lean...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:The oxidation of the side chain of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) into chenodeoxycholic acid has been studied in subcellular fractions of rat liver. The product was separated from the substrate by high pressure liquid chromatography and identified by gas-liquid chromatography-mass spectrome...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-06-01 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：:The activity of lipoprotein lipase isolated from rat postheparin plasma has been determined with synthetic lipids, in the presence and absence of apoprotein of the natural substrate very low density lipoprotein, as a function of medium ion-pair concentration of a number of different inorganic salts. The several kineti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hyp...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P026005
更新日期：2012-07-01 00:00:00
abstract：:Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice esta...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600177-JLR200
更新日期：2006-09-01 00:00:00
abstract：:Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies agai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
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
更新日期：2020-01-01 00:00:00
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
更新日期：2007-04-01 00:00:00
abstract：:Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino acid substituti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-09-01 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：:Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyt...
journal_title：Journal of lipid research
pub_type： 杂志文章,随机对照试验
doi：10.1194/jlr.P093013
更新日期：2019-06-01 00:00:00
abstract：:Rates of conversion of alpha-linolenic acid (alpha-LNA, 18:3n-3) to docosahexaenoic acid (DHA, 22:6n-3) by the mammalian brain and the brain's ability to upregulate these rates during dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) are unknown. To answer these questions, we measured conversion coefficie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600549-JLR200
更新日期：2007-05-01 00:00:00
abstract：:The objective of this study was to establish a new lipoprotein lipase (LPL) and hepatic lipase (HL) activity assay method. Seventy normal volunteers were recruited. Lipase activities were assayed by measuring the increase in absorbance at 546 nm due to the quinoneine dye. Reaction mixture-1 (R-1) contained dioleoylgly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700528-JLR200
更新日期：2008-07-01 00:00:00
abstract：:This report describes the gas-liquid chromatography-mass spectrometry (GLC-MS) of the trimethylsilyl ethers of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol with mono- or dihydroxy substitution in the side chain. Compounds with 24- and 25-unsaturation in the side chain were also studied. The gas-liquid chromatogr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-11-01 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：:Thioesterase superfamily member 1 (Them1; synonyms acyl-CoA thioesterase 11 and StarD14) is highly expressed in brown adipose tissue and limits energy expenditure in mice. Them1 is a putative fatty acyl-CoA thioesterase that comprises tandem hot dog-fold thioesterase domains and a lipid-binding C-terminal steroidogeni...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M029538
更新日期：2012-12-01 00:00:00
abstract：:We have developed a simplified and improved high performance liquid chromatography (HPLC) method for the detection and quantitation of tissue lipid using a new laser light-scattering detector (Varex model ELSD II). This detector has a limit of sensitivity of 50 ng for neutral lipid and 200 ng for most phospholipids wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:The biosynthesis of prostaglandins by isolated rat adrenocortical cells has been studied by determinations of products formed during incubations with labeled arachidonic acid and by radioimmunoassays. Analysis by thin-layer chromatographic separation of silicic acid column fractions indicated that PGE2, PGA2, (B2) and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:Compared with classic essential fatty acid deficiency or the feeding of a fat-free diet, little is known about specific linoleate deficiency in the rat. Carbon recycling into de novo lipogenesis has been reported to be an obligatory feature of linoleate metabolism in the liver, even in extreme linoleate deficiency (LA...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000671
更新日期：2020-06-01 00:00:00
abstract：:Using the "ghost method" previously applied to study the binding of palmitate to bovine serum albumin (BSA) (Bojesen, I. N., and E. Bojesen. 1992. J. Lipid Res. 33: 1327-1334) we have measured the water-phase concentrations of arachidonate (AR) and oleate (OL) in 165 mM KCl and in 165 mM NaCl, 2 mM phosphate buffer at...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Diet-induced changes in high density lipoprotein (HDL) density and size were studied in patas monkeys. When the animals were switched from a moderate fat-low cholesterol diet to a high fat-high cholesterol (HFHC) diet, the plasma apoA-I levels increased initially in all of the animals. The apoA-I levels remained eleva...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
