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Hanno C Resemann, Milena Lewandowska, Jasmin Gömann, Ivo Feussner
The moss Physcomitrella patens receives increased scientific interest since its genome was sequenced a decade ago. As a bryophyte, it represents the first group of plants that evolved in a terrestrial habitat still without a vascular system, that developed later in tracheophytes. It is easily transformable via homologous recombination, which enables the formation of targeted loss-of-function mutants. Even though genetics, development and life cycle in Physcomitrella are well studied nowadays, research on lipids in Physcomitrella is still underdeveloped...
January 30, 2019: Plant & Cell Physiology
B Garlito, T Portolés, W M A Niessen, J C Navarro, F Hontoria, Ó Monroig, I Varó, R Serrano
Gas chromatography coupled to a quadrupole time-of-flight mass analyzer (QTOF) with an atmospheric pressure chemical ionization (APCI) source has been tested to study the ionization and mass spectrometric behavior of long-chain and very long-chain polyunsaturated fatty acids (LC-PUFAs, C18-24 ; VLC-PUFAs, >C24 ). The protonated molecule ([M+H]+ ), measured at accurate mass, became the base peak of the spectrum for all the studied compounds and was promoted by the addition of water into the source. This fact overcame the existing difficulties for the identification of VLC-PUFAs when using an electron ionization source (EI)...
March 21, 2019: Analytica Chimica Acta
Saira A Khan, Robert T Jackson
Metabolic syndrome (MetS) is characterized by the accumulation of cardiovascular risk factors among men and women worldwide. The use of very long-chain polyunsaturated fatty acids (VLC PUFA) could potentially benefit individuals with MetS. The goal was to better understand the relationship between MetS and VLC PUFA in South Asian (SA) Americans who experience an elevated risk for heart disease. We analyzed a cross section of South Asian (SA) using the automated self-administered 24-hr recall (ASA24) and clinic data in a low-income SA in Maryland...
September 2018: Food Science & Nutrition
Martin-Paul Agbaga, Dana K Merriman, Richard S Brush, Todd A Lydic, Shannon M Conley, Muna I Naash, Shelley Jackson, Amina S Woods, Gavin E Reid, Julia V Busik, Robert E Anderson
Long-chain PUFAs (LC-PUFAs; C20-C22; e.g., DHA and arachidonic acid) are highly enriched in vertebrate retina, where they are elongated to very-long-chain PUFAs (VLC-PUFAs; C 28) by the elongation of very-long-chain fatty acids-4 (ELOVL4) enzyme. These fatty acids play essential roles in modulating neuronal function and health. The relevance of different lipid requirements in rods and cones to disease processes, such as age-related macular degeneration, however, remains unclear. To better understand the role of LC-PUFAs and VLC-PUFAs in the retina, we investigated the lipid compositions of whole retinas or photoreceptor outer segment (OS) membranes in rodents with rod- or cone-dominant retinas...
September 2018: Journal of Lipid Research
Melissa Conte, Josselin Lupette, Khawla Seddiki, Coline Meï, Lina-Juana Dolch, Valérie Gros, Caroline Barette, Fabrice Rébeillé, Juliette Jouhet, Eric Maréchal
Microalgae are a promising feedstock for the production of triacylglycerol (TAG) for a variety of potential applications, ranging from food and human health to biofuels and green chemistry. However, obtaining high TAG yields is challenging. A phenotypic assay for the accumulation of oil droplets was developed to screen a library of 1,200 drugs, annotated with pharmacology information, to select compounds that trigger TAG accumulation in the diatom Phaeodactylum tricornutum Using this screen, we identified 34 molecules acting in a dose-dependent manner...
June 2018: Plant Physiology
Luigi Donato, Concetta Scimone, Carmela Rinaldi, Pasquale Aragona, Silvana Briuglia, Angela D'Ascola, Rosalia D'Angelo, Antonina Sidoti
Purpose: Stargardt disease (STGD) is the most common form of inherited juvenile macular degeneration. It is inherited as autosomal recessive trait (STGD1), although STGD3 and STGD4 are inherited as autosomal dominant inheritance pattern. STGD3 is caused by mutations in the elongation of very long-chain fatty acids-like 4 (ELOVL4) gene encoding for a very long-chain fatty acid elongase. Mutations lead to a truncated Elovl4, lacking of a dilysine motif necessary for retention of transmembrane proteins in the endoplasmic reticulum...
February 1, 2018: Investigative Ophthalmology & Visual Science
Christian Schori, Martin-Paul Agbaga, Richard S Brush, Radha Ayyagari, Christian Grimm, Marijana Samardzija
Mutations in the elongation of very long chain fatty acid 4 (ELOVL4) gene cause Stargardt macular dystrophy 3 (STGD3), a rare, juvenile-onset, autosomal dominant form of macular degeneration. Although several mouse models have already been generated to investigate the link between the three identified disease-causing mutations in the ELOVL4 gene, none of these models recapitulates the early-onset cone photoreceptor cell death observed in the macula of STGD3 patients. To address this specifically, we investigated the effect of mutant ELOVL4 in a mouse model with an all-cone retina...
2018: PloS One
Xi Xie, Dauenpen Meesapyodsuk, Xiao Qiu
Thraustochytrium sp. 26185, a unicellular marine protist, synthesizes docosahexaenoic acid, an omega-3 very long chain polyunsaturated fatty acid (VLC-PUFAs), by a polyunsaturated fatty acid (PUFA) synthase comprising three large subunits with multiple catalytic dehydratase (DH) domains critical for introducing double bonds at the specific position of fatty acids. To investigate functions of these DH domains, one DH domain from subunit-A and two DH domains from subunit-C of the PUFA synthase were dissected and expressed as stand-alone enzymes in Escherichia coli...
January 2018: Applied Microbiology and Biotechnology
Bokkyoo Jun, Pranab K Mukherjee, Aram Asatryan, Marie-Audrey Kautzmann, Jessica Heap, William C Gordon, Surjyadipta Bhattacharjee, Rong Yang, Nicos A Petasis, Nicolas G Bazan
Docosahexaenoic acid (DHA, 22:6 n-3) is abundant in the retina and is enzymatically converted into pro-homeostatic docosanoids. The DHA- or eicosapentaenoic acid (EPA)-derived 26 carbon fatty acid is a substrate of elongase ELOVL4, which is expressed in photoreceptor cells and generates very long chain (≥C28) polyunsaturated fatty acids including n-3 (VLC-PUFAs,n-3). While ELOVL4 mutations are linked to vision loss and neuronal dysfunctions, the roles of VLC-PUFAs remain unknown. Here we report a novel class of lipid mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are oxygenated derivatives of VLC-PUFAs,n-3; we termed these mediators elovanoids (ELV)...
July 13, 2017: Scientific Reports
Min Jin, Óscar Monroig, Juan Carlos Navarro, Douglas R Tocher, Qi-Cun Zhou
Elongation of very long-chain fatty acid (Elovl) 4 proteins are important fatty acyl elongases that participate in the biosynthesis of long-chain (C20-24) and very long-chain (˃C24) polyunsaturated fatty acids (LC-PUFA and VLC-PUFA, respectively) in teleost fish, especially in marine species. Moreover, knowledge of Elovl4 and other elongases such as Elovl2 has contributed to an advanced understanding of the LC-PUFA biosynthetic pathway in marine fish. In the present study, elovl4a and elovl4b were cloned from black seabream Acanthopagrus schlegelii and functionally characterised using recombinant expression in yeast...
October 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Blake R Hopiavuori, Martin-Paul Agbaga, Richard S Brush, Michael T Sullivan, William E Sonntag, Robert E Anderson
We present here a quantitative molecular blueprint of the three major glycerophospholipid (GPL) classes, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE), in retina and six regions of the brain in C57Bl6 mice at 2, 10, and 26 months of age. We found an age-related increase in molecular species containing saturated and monoenoic FAs and an overall decrease in the longer-chain PUFA molecular species across brain regions, with loss of DHA-containing molecular species as the most consistent and dramatic finding...
April 2017: Journal of Lipid Research
Justine M Turner, Yves Sauvé, Miyoung Suh, Paul W Wales, Pamela Wizzard, Susan Goruk, Catherine J Field
BACKGROUND: Preterm neonates and those with intestinal failure require prolonged parenteral nutrition (PN) during a critical time of early central nervous system maturation. Conventional lipid emulsions fed to preterm neonates lack n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs; >20 carbon chain in length). Recently, fish oil lipid emulsions have been developed that provide both n-6 (ω-6) and n-3 LC-PUFAs, precursors of very long-chain PUFAs (VLC-PUFAs; >24 carbon chain in length)...
November 2016: Journal of Nutrition
Inna Khozin-Goldberg, Stefan Leu, Sammy Boussiba
Microalgae present a huge and still insufficiently tapped resource of very long-chain omega-3 and omega-6 polyunsaturated fatty acids (VLC-PUFA) for human nutrition and medicinal applications. This chapter describes the diversity of unicellular eukaryotic microalgae in respect to VLC-PUFA biosynthesis. Then, we outline the major biosynthetic pathways mediating the formation of VLC-PUFA by sequential desaturation and elongation of C18-PUFA acyl groups. We address the aspects of spatial localization of those pathways and elaborate on the role for VLC-PUFA in microalgal cells...
2016: Sub-cellular Biochemistry
Aruna Gorusupudi, Aihua Liu, Gregory S Hageman, Paul S Bernstein
The human retina is well-known to have unique lipid profiles enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and very long-chain polyunsaturated fatty acids (VLC-PUFAs) that appear to promote normal retinal structure and function, but the influence of diet on retinal lipid profiles in health and disease remains controversial. In this study, we examined two independent cohorts of donor eyes and related their retinal lipid profiles with systemic biomarkers of lipid intake. We found that serum and red blood cell lipids, and to a lesser extent orbital fat, are indeed excellent biomarkers of retinal lipid content and n-3/n-6 ratios in both the LC-PUFA and VLC-PUFA series...
March 2016: Journal of Lipid Research
Lea D Bennett, Robert E Anderson
Stargardt-like macular dystrophy-3 (STGD3) is a juvenile-onset disease caused by mutations in ELOVL4 (elongation of very long fatty acids-4). This gene product catalyzes the elongation of long chain saturated and polyunsaturated fatty acids (LC-FAs and LC-PUFAs) into very long chain FAs and PUFAs (VLC-FAs and VLC-PUFAs). These mutations cause a frame shift in the ELOVL4 transcript, introducing a premature stop codon that results in the translation of a truncated protein that has lost a C-terminus endoplasmic reticulum (ER) retention/retrieval signal...
2016: Advances in Experimental Medicine and Biology
Peter Barabas, Aruna Gorusupudi, Paul S Bernstein, David Krizaj
Stargardt type 3 macular degeneration is dependent on a dominant defect in a single gene, ELOVL4 (elongase of very long chain fatty acids 4). The encoded enzyme, ELOVL4, is required for the synthesis of very long chain polyunsaturated fatty acids (VLC-PUFAs), a rare class of > C24 lipids. In vitro expression studies suggest that mutated ELOVL4(STGD3) proteins fold improperly, resulting in ER stress and formation of cytosolic aggresomes of wild type and mutant ELOVL4. Although a number of mouse models have been developed to determine whether photoreceptor cell loss in STGD3 results from depletion of VLC-PUFAs, aggresome-dependent cell stress or a combination of these two factors, none of these models adequately recapitulates the disease phenotype in humans...
2016: Advances in Experimental Medicine and Biology
Sun Hee Kim, Kyung Hee Roh, Jong-Sug Park, Kwang-Soo Kim, Hyun Uk Kim, Kyeong-Ryeol Lee, Han-Chul Kang, Jong-Bum Kim
Reconstitution of nonnative, very-long-chain polyunsaturated fatty acid (VLC-PUFA) biosynthetic pathways in Arabidopsis thaliana was undertaken. The introduction of three primary biosynthetic activities to cells requires the stable coexpression of multiple proteins within the same cell. Herein, we report that C22 VLC-PUFAs were synthesized from C18 precursors by reactions catalyzed by Δ(6)-desaturase, an ELOVL5-like enzyme involved in VLC-PUFA elongation, and Δ(5)-desaturase. Coexpression of the corresponding genes (McD6DES, AsELOVL5, and PtD5DES) under the control of the seed-specific vicilin promoter resulted in production of docosapentaenoic acid (22:5 n-3) and docosatetraenoic acid (22:4 n-6) as well as eicosapentaenoic acid (20:5 n-3) and arachidonic acid (20:4 n-6) in Arabidopsis seeds...
2015: BioMed Research International
Minna Hiltunen, Ursula Strandberg, Markku Keinänen, Sami Taipale, Paula Kankaala
We studied the copepod Limnocalanus macrurus for seasonal variation in the composition of fatty acids, wax esters and sterols in large boreal lakes, where it occurs as a glacial-relict. Vast wax ester reserves of Limnocalanus were accumulated in a period of only two months, and comprised mono- and polyunsaturated fatty acids (PUFA) and saturated fatty alcohols. In winter, the mobilization of wax esters was selective, and the proportion of long-chain polyunsaturated wax esters declined first. PUFA accounted for >50% of all fatty acids throughout the year reaching up to ca...
September 2014: Lipids
Sun Hee Kim, Kyung Hee Roh, Kwang-Soo Kim, Hyun Uk Kim, Kyeong-Ryeol Lee, Han-Chul Kang, Jong-Bum Kim
The introduction of novel traits to cells often requires the stable coexpression of multiple genes within the same cell. Herein, we report that C22 very long-chain polyunsaturated fatty acids (VLC-PUFAs) were synthesized from C18 precursors by reactions catalyzed by delta 6-desaturase, an ELOVL5 involved in VLC-PUFA elongation, and delta 5-desaturase. The coexpression of McD6DES, AsELOVL5, and PtD5DES encoding the corresponding enzymes, produced docosatetraenoic acid (C22:4 n-6) and docosapentaenoic acid (C22:5 n-3), as well as arachidonic acid (C20:4 n-6) and eicosapentaenoic acid (C20:5 n-3) in the methylotrophic yeast Pichia pastoris...
September 2014: Biotechnology Letters
Roger Huerlimann, Eike J Steinig, Heather Loxton, Kyall R Zenger, Dean R Jerry, Kirsten Heimann
Very long-chain polyunsaturated fatty acids (VLC-PUFAs) are important dietary requirements for maintaining human health. Many marine microalgae are naturally high in ω-3 VLC-PUFAs, however, the molecular mechanisms underpinning fatty acid (FA) desaturation and elongation in algae are poorly understood. An advanced molecular understanding would facilitate improvements of this nascent industry. We aimed to investigate expression responses of four front-end fatty acid desaturase genes and downstream effects on FA profiles to nitrogen limitation and cultivation growth stage in Isochrysis aff...
July 15, 2014: Gene
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