Enantioselective Analysis of 2- and 3-Hydroxy Fatty Acids in Food Samples

Jenske, Ramona; Vetter, Walter

doi:10.1021/jf802772a

Cited by 25 publications

(21 citation statements)

References 27 publications

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“…A consistent distribution of positive and negative Δδ H values (Δδ H = δ S − δ R ) around C-3 allowed the assignment of R -configuration for C-3 position (Figure 3) [23]. This result was also supported by the literature reviews, as ( R )-3-hydroxy fatty acid displays negative molecular rotation in MeOH [24,25]. The absolute stereochemistry at 3-hydroxy position of the fatty acid in 2 was determined to possess R configuration by the comparison of optical rotation value with that of fatty acid in 1 (Supplementary Information).…”

Section: Resultssupporting

confidence: 56%

Gageostatins A–C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis

Tareq

Lee

et al. 2014

Marine Drugs

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Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A–C (1–3), consisting of hepta-peptides and new 3-β-hydroxy fatty acids from the fermentation broth of a marine-derived bacterium Bacillus subtilis. Their structures were elucidated by analyzing a combination of extensive 1D, 2D NMR spectroscopic data and high resolution ESIMS data. Fatty acids, namely 3-β-hydroxy-11-methyltridecanoic and 3-β-hydroxy-9,11-dimethyltridecanoic acids were characterized in lipopeptides 1 and 2, respectively, whereas an unsaturated fatty acid (E)-7,9-dimethylundec-2-enoic acid was assigned in 3. The 3R configuration of the stereocenter of 3-β-hydroxy fatty acids in 1 and 2 was established by Mosher’s MTPA method. The absolute stereochemistry of amino acid residues in 1–3 was ascertained by acid hydrolysis followed by Marfey’s derivatization studies. Gageostatins 1–3 exhibited good antifungal activities with MICs values of 4–32 µg/mL when tested against pathogenic fungi (R. solani, B. cinerea and C. acutatum) and moderate antibacterial activity against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) with MICs values of 8–64 µg/mL. Futhermore, gageostatins 1–3 displayed cytotoxicity against six human cancer cell lines with GI50 values of 4.6–19.6 µg/mL. It is also noteworthy that mixed compounds 1+2 displayed better antifungal and cytotoxic activities than individuals.

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Section: Resultssupporting

confidence: 56%

Gageostatins A–C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis

Tareq

Lee

et al. 2014

Marine Drugs

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“…Moreover, the presence of another FA 2-hydroxylase in peroxisome cannot be excluded. 2-Hydroxylation generates a chiral carbon in fatty acids, and both enantiomers are detected in brain samples (53), suggesting the presence of multiple 2-hydroxylases with opposite stereospecificities. In this respect, it would be informative to gain a better understanding of the stereospecificity of FA2H.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid 2-Hydroxylase Mediates Diffusional Mobility of Raft-associated Lipids, GLUT4 Level, and Lipogenesis in 3T3-L1 Adipocytes

Guo

Zhou

Pryse

et al. 2010

Journal of Biological Chemistry

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Straight chain fatty acid ␣-oxidation increases during differentiation of 3T3-L1 adipocytes, leading to a marked accumulation of odd chain length fatty acyl moieties. Potential roles of this pathway in adipocyte differentiation and lipogenesis are unknown. Mammalian fatty acid 2-hydroxylase (FA2H) was recently identified and suggested to catalyze the initial step of straight chain fatty acid ␣-oxidation. Accordingly, we examined whether FA2H modulates adipocyte differentiation and lipogenesis in mature adipocytes. FA2H level markedly increases during differentiation of 3T3-L1 adipocytes, and small interfering RNAs against FA2H inhibit the differentiation process. In mature adipocytes, depletion of FA2H inhibits basal and insulin-stimulated glucose uptake and lipogenesis, which are partially rescued by the enzymatic product of FA2H, 2-hydroxy palmitic acid. Expression of fatty-acid synthase and SCD1 was decreased in FA2H-depleted cells, and levels of GLUT4 and insulin receptor proteins were reduced. 2-Hydroxy fatty acids are enriched in cellular sphingolipids, which are components of membrane rafts. Accelerated diffusional mobility of raft-associated lipids was shown to enhance degradation of GLUT4 and insulin receptor in adipocytes. Consistent with this, depletion of FA2H appeared to increase raft lipid mobility as it significantly accelerated the rates of fluorescence recovery after photobleaching measurements of lipid rafts labeled with Alexa 488-conjugated cholera toxin subunit B. Moreover, the enhanced recovery rates were partially reversed by treatment with 2-hydroxy palmitic acid. In conclusion, our findings document the novel role of FA2H in adipocyte lipogenesis possibly by modulation of raft fluidity and level of GLUT4.In addition to mitochondrial ␤-oxidation, fatty acids (FA) 2 can also be oxidized in peroxisomes, where they can undergo ␤-as well as ␣-oxidation. Peroxisomal ␣-oxidation produces fatty acyl moieties with one less carbon (odd chain length) without generating acetyl-CoA (1). It is well known that peroxisomal ␣-oxidation is important for catabolism of branched-chain FA and also for very long chain FA (2). Its contribution to catabolism of other long chain FA is not known, so its role in whole cell energy homeostasis remains unclear. There is evidence for up-regulation of FA ␣-oxidation during the preadipocyte to adipocyte transition as cells begin accumulating lipids. Using electrospray ionization-mass spectrometry and gas chromatography-coupled mass spectrometry, we and others demonstrated during differentiation of 3T3-L1 cells a marked increase in activity of peroxisomal FA ␣-oxidation, which was reflected in accumulation of odd chain length acyl moieties in major lipid species (3, 4). The underlying mechanisms for this change and the functions of the ␣-oxidation pathway in adipocyte differentiation and lipid metabolism in mature adipocytes have not been explored.Although straight chain FA ␣-oxidation was first reported in 1964 (5), a detailed understanding of the enzymatic pathway is sti...

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“…After spiking 500 pmol of each component of ceramide/sphingoid internal standards mixture I (Avanti Polar Lipids, LM-6002), lipids were extracted as 2-OH FAs. Wool wax 2-OH FAs are found exclusively in the ( R ) form, whereas in bacterial lipopolysaccharides, ( S )-2 -OH FAs are the major form ( 15,16 ). Most food and animal tissue samples, including fat (suet) ( 17 ), have both enantiomers ( 16 ).…”

Section: Lipid Extraction and Analysis Of Sphingolipids By Esi Msmentioning

confidence: 99%

“…Wool wax 2-OH FAs are found exclusively in the ( R ) form, whereas in bacterial lipopolysaccharides, ( S )-2 -OH FAs are the major form ( 15,16 ). Most food and animal tissue samples, including fat (suet) ( 17 ), have both enantiomers ( 16 ). However, there is lack of information on which enantiomer is generated by FA2H and on whether both enantiomers are biologically active.…”

Section: Lipid Extraction and Analysis Of Sphingolipids By Esi Msmentioning

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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Enantioselective Analysis of 2- and 3-Hydroxy Fatty Acids in Food Samples

Cited by 25 publications

References 27 publications

Gageostatins A–C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis

Gageostatins A–C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis

Fatty Acid 2-Hydroxylase Mediates Diffusional Mobility of Raft-associated Lipids, GLUT4 Level, and Lipogenesis in 3T3-L1 Adipocytes

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

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