当前位置： SCI文献检索 > JOURNAL OF LIPID RESEARCH期刊下所有文献 > Distinguishing the differences in β-glycosylceramidase folds, dynamics, and actions informs therapeutic uses.

Distinguishing the differences in β-glycosylceramidase folds, dynamics, and actions informs therapeutic uses.

Abstract：

:Glycosyl hydrolases (GHs) are carbohydrate-active enzymes that hydrolyze a specific β-glycosidic bond in glycoconjugate substrates; β-glucosidases degrade glucosylceramide, a ubiquitous glycosphingolipid. GHs are grouped into structurally similar families that themselves can be grouped into clans. GH1, GH5, and GH30 glycosidases belong to clan A hydrolases with a catalytic (β/α)8 TIM barrel domain, whereas GH116 belongs to clan O with a catalytic (α/α)6 domain. In humans, GH abnormalities underlie metabolic diseases. The lysosomal enzyme glucocerebrosidase (family GH30), deficient in Gaucher disease and implicated in Parkinson disease etiology, and the cytosol-facing membrane-bound glucosylceramidase (family GH116) remove the terminal glucose from the ceramide lipid moiety. Here, we compare enzyme differences in fold, action, dynamics, and catalytic domain stabilization by binding site occupancy. We also explore other glycosidases with reported glycosylceramidase activity, including human cytosolic β-glucosidase, intestinal lactase-phlorizin hydrolase, and lysosomal galactosylceramidase. Last, we describe the successful translation of research to practice: recombinant glycosidases and glucosylceramide metabolism modulators are approved drug products (enzyme replacement therapies). Activity-based probes now facilitate the diagnosis of enzyme deficiency and screening for compounds that interact with the catalytic pocket of glycosidases. Future research may deepen the understanding of the functional variety of these enzymes and their therapeutic potential.

journal_name

J Lipid Res

journal_title

Journal of lipid research

authors

Ben Bdira F,Artola M,Overkleeft HS,Ubbink M,Aerts JMFG

doi

10.1194/jlr.R086629

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

2262-2276

issue

12

eissn

0022-2275

issn

1539-7262

pii

jlr.R086629

journal_volume

59

pub_type

杂志文章

相关文献

JOURNAL OF LIPID RESEARCH文献大全
  • On the analysis of long-chain alkane diols and glycerol ehters in biochemical studies.

    abstract：:The chromatographic behavior of 1,2-, 1,3-, 1,4-, and 1,12-long-chain alkane diols and 1-O-alkylglycerols and their derivatives has been compared. Thin-layer chromatography on Silica Gel G gives poor separations of the 1,2-, 1,3-, and 1,4-alkane diols, O-alkylglycerols, and some of their isopropylidene derivatives. Ho...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Blank ML,Cress EA,Stephens N,Snyder F

    更新日期：1971-09-01 00:00:00

  • Ceramide and sphingomyelin species of fibroblasts and neurons in culture.

    abstract：:The ceramide (Cer) and sphingomyelin (SM) species of cultured differentiated rat cerebellar granule cells and human fibroblasts were characterized by electrospray ionization-mass spectrometry. We identified 35 different species of Cer and 18 species of SM in human fibroblasts, and 35 different species of Cer and 9 spe...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M600344-JLR200

    authors： Valsecchi M,Mauri L,Casellato R,Prioni S,Loberto N,Prinetti A,Chigorno V,Sonnino S

    更新日期：2007-02-01 00:00:00

  • CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice.

    abstract：:Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M037812

    authors： Nassir F,Adewole OL,Brunt EM,Abumrad NA

    更新日期：2013-11-01 00:00:00

  • Apolipoprotein A-I assayed in human serum by isotope dilution as a potential standard for immunoassay.

    abstract：:We measured the amount of apoA-I in serum by isotope dilution, finding 1.33 mg/ml (standard deviation 0.177) in six normolipidemic, healthy subjects. We developed this method by adapting published techniques to purify apoA-I from 3 ml of serum in two steps: density gradient ultracentrifugation and high performance liq...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Weech PK,Jewer D,Marcel YL

    更新日期：1988-01-01 00:00:00

  • beta-sitosterol: esterification by intestinal acylcoenzyme A: cholesterol acyltransferase (ACAT) and its effect on cholesterol esterification.

    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：

    authors： Field FJ,Mathur SN

    更新日期：1983-04-01 00:00:00

  • Genetic analysis of abdominal fat distribution in SM/J and A/J mice.

    abstract：:Each abdominal fat depot, such as mesenteric or epididymal, differently contributes to the development of insulin resistance. The aim of this study was to identify the genetic regions that contribute to fat accumulation in epididymal/mesenteric fat and to examine whether or not the genetic regions that affect glucose ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M009563

    authors： Kobayashi M,Ohno T,Hada N,Fujiyoshi M,Kuga M,Nishimura M,Murai A,Horio F

    更新日期：2010-12-01 00:00:00

  • Fractionation of human serum lipoproteins by single-spin gradient ultracentrifugation: quantification of apolipoproteins B and A-1 and lipid components.

    abstract：:A sensitive and reproducible method has been developed for separation of the major serum lipoproteins from 1 ml or less of human serum by isopycnic density gradient ultracentrifugation. The serum, applied to a step gradient (total volume 12.8 ml), was spun for 48 hr at 38,000 rpm at 10 degrees C and, in each of the fr...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Foreman JR,Karlin JB,Edelstein C,Juhn DJ,Rubenstein AH,Scanu AM

    更新日期：1977-11-01 00:00:00

  • Differential regulation of apolipoprotein B secretion from HepG2 cells by two HMG-CoA reductase inhibitors, atorvastatin and simvastatin.

    abstract：:The concept that hepatic cholesterol synthesis regulates hepatocyte assembly and secretion of apoB-containing lipoproteins remains controversial. The present study was carried out in HepG2 cells to examine the regulation of apoB secretion by the HMG-CoA reductase inhibitor atorvastatin. ApoB accumulation in the media ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Wilcox LJ,Barrett PH,Huff MW

    更新日期：1999-06-01 00:00:00

  • Detection of monohydroxy "bile" acids in the brains of guinea pigs afflicted with experimental allergic encephalomyelitis.

    abstract：:3alpha-Hydroxy-5-cholanoic acid (lithocholic acid) and some unidentified acids (one of them perhaps 3-hydroxy-cholest-5-en-26-oic acid) have been detected in the brains of guinea pigs afflicted with experimental "allergic" encephalomyelitis. None of the acids could be identified in comparable amounts of brain tissue f...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Naqvi SH,Herndon BL,Kelley MT,Bleisch V,Aexel RT,Nicholas HJ

    更新日期：1969-01-01 00:00:00

  • Native LDL potentiate TNF alpha and IL-8 production by human mononuclear cells.

    abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.m100254-jlr200

    authors： Netea MG,Kullberg BJ,Demacker PN,Jacobs LE,Verver-Jansen TJ,Hijmans A,van Tits LH,Hoenderop JG,Willems PH,Van der Meer JW,Stalenhoef AF

    更新日期：2002-07-01 00:00:00

  • Oxysterol efflux from macrophage foam cells: the essential role of acceptor phospholipid.

    abstract：:Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic lesions and may play an active role in lesion development. For example, 7-ketocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxysterols may promote foam cell formation in ath...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Gelissen IC,Rye KA,Brown AJ,Dean RT,Jessup W

    更新日期：1999-09-01 00:00:00

  • Hydrolysis of primary and secondary esters of glycerol by pancreatic juice.

    abstract：:The relative rates of hydrolysis of the secondary ester in glycerol 1,3-benzylidene 2-oleate and in glycerol 1,3-dihexadecyl ether 2-oleate, and of the primary and secondary esters in triolein were determined. Both unaltered and selectively inactivated rat pancreatic juice were used as sources of enzyme. It was found ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Mattson FH,Volpenhein RA

    更新日期：1968-01-01 00:00:00

  • Suppression of adipose lipolysis by long-chain fatty acid analogs.

    abstract：:Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M022673

    authors： Kalderon B,Azazmeh N,Azulay N,Vissler N,Valitsky M,Bar-Tana J

    更新日期：2012-05-01 00:00:00

  • PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain.

    abstract：:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans. PCSK9 has also been shown to regulate the levels of additional membrane-bound proteins in vitro, including the very low-density lipoprotein receptor (VLDLR), apol...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M006635

    authors： Liu M,Wu G,Baysarowich J,Kavana M,Addona GH,Bierilo KK,Mudgett JS,Pavlovic G,Sitlani A,Renger JJ,Hubbard BK,Fisher TS,Zerbinatti CV

    更新日期：2010-09-01 00:00:00

  • Effects of n-3 fatty acids on the NMR profile of plasma lipoproteins.

    abstract：:The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were det...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Bell JD,Barnard ML,Parkes HG,Thomas EL,Brennan CH,Cunnane SC,Dagnelie PC

    更新日期：1996-08-01 00:00:00

  • Density gradient characterization of the high density lipoproteins in cholesterol-fed hyper- and hyporesponding patas monkeys (Erythrocebus patas).

    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：

    authors： Melchior GW,Baker HN,Abee CR,Roheim PS

    更新日期：1984-09-01 00:00:00

  • Novel phage display-derived mycolic acid-specific antibodies with potential for tuberculosis diagnosis.

    abstract：:Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker. Mycolic a...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.D036137

    authors： Chan CE,Zhao BZ,Cazenave-Gassiot A,Pang SW,Bendt AK,Wenk MR,MacAry PA,Hanson BJ

    更新日期：2013-10-01 00:00:00

  • Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study.

    abstract：:Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was perfor...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Lehtimäki T,Moilanen T,Viikari J,Akerblom HK,Ehnholm C,Rönnemaa T,Marniemi J,Dahlen G,Nikkari T

    更新日期：1990-03-01 00:00:00

  • Enzymatic sulfation of glycochenodeoxycholic acid by tissue fractions from adult hamsters.

    abstract：:Using a radiometric assay with glycochenodeoxycholic acid as substrate, bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase activity was found in 105,000 g supernatant fractions of liver, proximal intestine, and adrenal gland homogenates from adult hamsters. Optimum conditions for measurement of the hepat...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Barnes S,Burhol PG,Zander R,Haggstrom G,Settine RL,Hirschowitz BI

    更新日期：1979-11-01 00:00:00

  • Relationship of the parameters of body cholesterol metabolism with plasma levels of HDL cholesterol and the major HDL apoproteins.

    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：

    authors： Blum CB,Dell RB,Palmer RH,Ramakrishnan R,Seplowitz AH,Goodman DS

    更新日期：1985-09-01 00:00:00

  • Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver.

    abstract：:Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpr...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M046961

    authors： Moffat C,Bhatia L,Nguyen T,Lynch P,Wang M,Wang D,Ilkayeva OR,Han X,Hirschey MD,Claypool SM,Seifert EL

    更新日期：2014-12-01 00:00:00

  • Surface study of apoB1694-1880, a sequence that can anchor apoB to lipoproteins and make it nonexchangeable.

    abstract：:Apolipoprotein B (apoB) is a nonexchangeable apolipoprotein. During lipoprotein assembly, it recruits phospholipids and triacylglycerols (TAG) into TAG-rich lipoprotein particles. It remains bound to secreted lipoproteins during lipid metabolism in plasma. The beta1 region (residues 827-1880) of apoB has a high amphip...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M900040-JLR200

    authors： Wang L,Martin DD,Genter E,Wang J,McLeod RS,Small DM

    更新日期：2009-07-01 00:00:00

  • ApoC-III ASO promotes tissue LPL activity in the absence of apoE-mediated TRL clearance.

    abstract：:Hypertriglyceridemia results from accumulation of triglyceride (TG)-rich lipoproteins (TRLs) in the circulation and is associated with increased CVD risk. ApoC-III is an apolipoprotein on TRLs and a prominent negative regulator of TG catabolism. We recently established that in vivo apoC-III predominantly inhibits LDL ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M093740

    authors： Ramms B,Patel S,Nora C,Pessentheiner AR,Chang MW,Green CR,Golden GJ,Secrest P,Krauss RM,Metallo CM,Benner C,Alexander VJ,Witztum JL,Tsimikas S,Esko JD,Gordts PLSM

    更新日期：2019-08-01 00:00:00

  • Rat heart cannot synthesize docosahexaenoic acid from circulating alpha-linolenic acid because it lacks elongase-2.

    abstract：:The extent to which the heart can convert alpha-linolenic acid (alpha-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled alpha-LNA and a kinetic fatty acid model. [1-(14)C]alpha-LNA was infused intravenously for 5 min in unanesthetized rats that had been f...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M800093-JLR200

    authors： Igarashi M,Ma K,Chang L,Bell JM,Rapoport SI

    更新日期：2008-08-01 00:00:00

  • Acetyl-L-carnitine flux to lipids in cells estimated using isotopomer spectral analysis.

    abstract：:Acetyl-L-carnitine is known as a reservoir of activated acetyl units and as a modulator of metabolic function. The objective of this study was to quantify the fate of the acetyl moiety of acetyl-L-carnitine in lipogenic pathways. Lipogenesis was studied in an adipocyte model, differentiated 3T3-L1 cells, and a hepatom...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Lligona-Trulla L,Arduini A,Aldaghlas TA,Calvani M,Kelleher JK

    更新日期：1997-07-01 00:00:00

  • Appraisal of hepatic lipase and lipoprotein lipase activities in mice.

    abstract：:A variety of methods are currently used to analyze HL and LPL activities in mice. In search of a simple methodology, we analyzed mouse preheparin and postheparin plasma LPL and HL activities using specific polyclonal antibodies raised in rabbit against rat HL (anti-HL) and in goat against rat LPL (anti-LPL). As an alt...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.D700021-JLR200

    authors： Dallinga-Thie GM,Zonneveld-de Boer AJ,van Vark-van der Zee LC,van Haperen R,van Gent T,Jansen H,De Crom R,van Tol A

    更新日期：2007-12-01 00:00:00

  • Gas--liquid chromatography--mass spectrophotometry of hydroxylated octadecanols derived from hydroxylated stearic acids.

    abstract：:A gas-liquid chromatographic-mass spectrometric method of determining the position of oxygen atoms on polyfunctional fatty acids has been explored. The method consists of reduction of keto, hydroperoxy, epoxy, and carboxylic acid groups with LiAlH(4) to the corresponding alcohols; trimethylsilylation with bis(trimethy...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Esselman WJ,Clagett CO

    更新日期：1969-03-01 00:00:00

  • Effects of sphingomyelinase and sphingosine on arterial vasomotor regulation.

    abstract：:The sphingomyelin pathway is an important signal transduction system regulating various cellular functions. However, little is known about the effect of sphingomyelin metabolites on vasomotor function. We examined the vascular effects of sphingomyelin, sphingosine, and sphingomyelinase (SPMase) in vitro. In pig corona...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Murohara T,Kugiyama K,Ohgushi M,Sugiyama S,Ohta Y,Yasue H

    更新日期：1996-07-01 00:00:00

  • Genetic analysis of cholesterol accumulation in inbred mice.

    abstract：:Genetic linkage analysis in the laboratory mouse identified chromosomal regions containing genes that contribute to cholesterol accumulation in the liver and plasma. Comparisons between five inbred strains of mice obtained from the Jackson Laboratory (DBA/2, AKR, C57BL/6, SJL, and 129P3) revealed a direct correlation ...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：

    authors： Schwarz M,Davis DL,Vick BR,Russell DW

    更新日期：2001-11-01 00:00:00

  • Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice.

    abstract：:Our previous studies have shown accumulation of GM2 ganglioside during ethanol-induced neurodegeneration in the developing brain, and GM2 elevation has also been reported in other brain injuries and neurodegenerative diseases. Using GM2/GD2 synthase KO mice lacking GM2/GD2 and downstream gangliosides, the current stud...

    journal_title：Journal of lipid research

    pub_type： 杂志文章

    doi：10.1194/jlr.M056580

    authors： Saito M,Wu G,Hui M,Masiello K,Dobrenis K,Ledeen RW,Saito M

    更新日期：2015-08-01 00:00:00