Membrane bilayer properties of sphingomyelins with amide-linked 2- or 3-hydroxylated fatty acids

Ekholm, Oscar; Jaikishan, Shishir; Lönnfors, Max; Nyholm, Thomas K.M.; Slotte, J. Peter

doi:10.1016/j.bbamem.2010.12.006

Cited by 22 publications

(13 citation statements)

References 43 publications

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“…This report is in line with our observation that the OH group does not significantly alter the partitioning of the Gb 3 species in phase-separated GUVs.H owever,i nap revious study,wefound that the 2-OH group influences the fraction of l o phase in phase-separated supported lipid bilayers. [21] In the case of the hydroxylated C 24:0 fatty acid, the l o fraction was smaller than that of the nonhydroxylated species.S lotte and co-workers [47] showed that the 2-OH group increases the hydration in the membrane interface and decreases the affinity of as phingolipid for sterols.T he same was found by Lingwood et al [48] and Yahi et al [49] and implies that the The partition of the Gb 3 species harboring asaturated fatty acid (C 24:0 ) were compared with that with an attached unsaturated fatty acid (C 24:1 ). The mean values are given as ared star,w hile the red lines show the median value (Table 1).…”

Section: Angewandte Chemiementioning

confidence: 99%

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

et al. 2019

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The receptor lipid Gb3 is responsible for the specific internalization of Shiga toxin (STx) into cells. The head group of Gb3 defines the specificity of STx binding, and the backbone with different fatty acids is expected to influence its localization within membranes impacting membrane organization and protein internalization. To investigate this influence, a set of Gb3 glycosphingolipids labeled with a BODIPY fluorophore attached to the head group was synthesized. C24 fatty acids, saturated, unsaturated, α‐hydroxylated derivatives, and a combination thereof, were attached to the sphingosine backbone. The synthetic Gb3 glycosphingolipids were reconstituted into coexisting liquid‐ordered (lo)/liquid‐disordered (ld) giant unilamellar vesicles (GUVs), and STx binding was verified by fluorescence microscopy. Gb3 with the C24:0 fatty acid partitioned mostly in the lo phase, while the unsaturated C24:1 fatty acid distributes more into the ld phase. The α‐hydroxylation does not influence its partitioning.

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Section: Angewandte Chemiementioning

confidence: 99%

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

et al. 2019

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“…Individual colonies were isolated using cloning cylinders Scheme. 1 and 2-OH FAMEs were prepared by methylation prior to separation on a silica plate. The isolated 2-OH FAMEs were then derivatized with ( R )-MTPA-Cl and analyzed by GC-NCI-MS. As shown in Fig.…”

Section: Generation Of Chinese Hamster Ovary Cell Line Stably Over-exmentioning

confidence: 99%

“…FA hydroxylation alters the packing structures of membrane microdomains and thus could regulate cellular functions of membrane-associated proteins ( 1 ). FA 2-hydroxylase (Sigma) and transferred to 24-well plates in duplicate.…”

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confidence: 99%

Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers

Guo

Zhang

Zhou

et al. 2012

Journal of Lipid Research

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(FA2H) is a recently identifi ed NAD(P)H-dependent enzyme that catalyzes the hydroxylation of FA at the C-2 position to produce 2-hydroxy FAs (2-OH FAs) ( Scheme 1 ) Scheme 1( 2, 3 ). In addition to undergoing ␣ oxidation to form oddchain-length FAs ( 4 ), the FA2H-generated 2-OH FAs are incorporated into a long-chain sphingosine base via an amide bond to generate 2-hydroxy sphingolipids (2-OH sphingolipids) ( Scheme 1 ) ( 5 ). The 2-OH sphingolipids are important components of plasma membrane lipid rafts, which host a variety of signaling and traffi cking events. Specifi c functions of 2-OH sphingolipids in membrane endocytosis were fi rst demonstrated in Saccharomyces cerevisiae yeast strains with defective SCS7/FA2H ( 6, 7 ). Recent genetic studies suggest a critical role of FA2H and possibly 2-OH sphingolipids in multiple neurodegenerative diseases. Loss of FA2H in mice causes signifi cant demyelination and profound axonal loss ( 8,9 ). Mutations in the FA2H gene in humans are associated with leukodystrophy ( 10 ), spastic paraplegia ( 11 ), and neurodegeneration with brain iron accumulation ( 12 ). FA2H may also play a signifi cant role in metabolism. We recently showed decreased levels of glucose transporter 4 (GLUT4) proteins and thus cellular glucose uptake in FA2H knockdown adipocytes ( 13 ). A recent study also suggested a role of FA2H in synthesis of specifi c sebaceous gland or sebum lipids and in regulating the hair follicle homeostasis ( 14 ).2-OH FAs are chiral due to the asymmetric carbon bearing the hydroxyl group, and a specifi c 2-hydroxylase usually generates enantiopure products. Biological samples and diets therefore have different enantio-enrichments of Abstract FA 2-hydroxylase (FA2H) is an NAD(P)H-dependent enzyme that initiates FA ␣ oxidation and is also responsible for the biosynthesis of 2-hydroxy FA (2-OH FA)-containing sphingolipids in mammalian cells. The 2-OH FA is chiral due to the asymmetric carbon bearing the hydroxyl group. Our current study performed stereochemistry investigation and showed that FA2H is stereospecifi c for the production of ( R )-enantiomers. FA2H knockdown in adipocytes increases diffusional mobility of raft-associated lipids, leading to reduced GLUT4 protein level, glucose uptake, and lipogenesis. The effects caused by Manuscript received 23 February 2012 and in revised form 29 March 2012. Published, JLR Papers in Press, April 19, 2012 DOI 10.1194 Stereospecifi city of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers Abbreviations: Cer, ceramide; CHO, Chinese hamster ovary; CTxB, cholera toxin subunit B; D, diffusion coeffi cient; FA2H, FA 2-hydroxylase; FAME, FA methyl ester; FRAP, fl uorescence recovery after photobleaching; GLUT4, glucose transporter 4; HexCer, hexosylceramide; Mf, mobile fraction; MTPA, ␣ -methoxy-␣ -trifl uoromethylphenylacetyl; NCI-MS, negative chemical ionization mass spectrometry; NL, neutral loss; 2-OH Cer, 2-hydroxy ceramide; 2-OH FA, 2-hydroxy FA; 2-OH PA, 2-OH palmitic acid; 2-OH sphingo...

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“…In the case of the hydroxylated C 24:0 fatty acid, the l o fraction was smaller than that of the nonhydroxylated species. Slotte and co‐workers showed that the 2‐OH group increases the hydration in the membrane interface and decreases the affinity of a sphingolipid for sterols. The same was found by Lingwood et al .…”

Section: Resultsmentioning

confidence: 90%

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

et al. 2019

View full text Add to dashboard Cite

The receptor lipid Gb 3 is responsible for the specific internalization of Shiga toxin (STx) into cells.The head group of Gb 3 defines the specificity of STx binding,and the backbone with different fatty acids is expected to influence its localization within membranes impacting membrane organization and protein internalization. To investigate this influence,aset of Gb 3 glycosphingolipids labeled with aB ODIPY fluorophore attached to the head group was synthesized. C 24 fatty acids, saturated, unsaturated, a-hydroxylated derivatives,and acombination thereof,w ere attached to the sphingosine backbone. The synthetic Gb 3 glycosphingolipids were reconstituted into coexisting liquid-ordered (l o )/liquid-disordered (l d )g iant unilamellar vesicles (GUVs), and STx binding was verified by fluorescence microscopy. Gb 3 with the C 24:0 fatty acid partitioned mostly in the l o phase,w hile the unsaturated C 24:1 fatty acid distributes more into the l d phase.T he a-hydroxylation does not influence its partitioning.

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Membrane bilayer properties of sphingomyelins with amide-linked 2- or 3-hydroxylated fatty acids

Cited by 22 publications

References 43 publications

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

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Membrane bilayer properties of sphingomyelins with amide-linked 2- or 3-hydroxylated fatty acids

Cited by 22 publications

References 43 publications

Synthesis of Gb3 Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Synthesis of Gb3 Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers

Synthesis of Gb3 Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

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Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles

Synthesis of Gb₃ Glycosphingolipids with Labeled Head Groups: Distribution in Phase‐Separated Giant Unilamellar Vesicles