scholarly journals Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 356 ◽  
Author(s):  
Aleksandra Czumaj ◽  
Tomasz Śledziński
Keyword(s):  
Fatty Acid ◽  
Unsaturated Fatty Acid ◽  
Acyl Chain ◽  
Fatty Acid Desaturase ◽  
Fatty Acid Desaturases ◽  
Qualitative And Quantitative ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
And Function ◽  
Expression And Activity

Polyunsaturated fatty acids (PUFAs) are considered one of the most important components of cells that influence normal development and function of many organisms, both eukaryotes and prokaryotes. Unsaturated fatty acid desaturases play a crucial role in the synthesis of PUFAs, inserting additional unsaturated bonds into the acyl chain. The level of expression and activity of different types of desaturases determines profiles of PUFAs. It is well recognized that qualitative and quantitative changes in the PUFA profile, resulting from alterations in the expression and activity of fatty acid desaturases, are associated with many pathological conditions. Understanding of underlying mechanisms of fatty acid desaturase activity and their functional modification will facilitate the development of novel therapeutic strategies in diseases associated with qualitative and quantitative disorders of PUFA.

scholarly journals Cyanophage-encoded lipid-desaturases: oceanic distribution, diversity and function

2017 ◽  
Author(s):  
Sheila Roitman ◽  
Ellen Hornung ◽  
José Flores-Uribe ◽  
Itai Sharon ◽  
Ivo Feussner ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Desaturase ◽  
Long Chain Fatty Acids ◽  
Fatty Acid Desaturases ◽  
Coping With Stress ◽  
Photosynthetic Organisms ◽  
Metabolic Genes ◽  
Fatty Acid Profiling ◽  
And Function ◽  
Auxiliary Metabolic Genes

AbstractCyanobacteria are among the most abundant photosynthetic organisms in the oceans; viruses infecting cyanobacteria (cyanophages) can alter cyanobacterial populations, and therefore affect the local food web and global biochemical cycles. These phages carry auxiliary metabolic genes (AMGs), which rewire various metabolic pathways in the infected host cell, resulting in increased phage fitness. Coping with stress resulting from photodamage appears to be a central necessity of cyanophages, yet the overall mechanism is poorly understood. Here we report a novel, widespread cyanophage AMG, encoding a fatty acid desaturase (FAD), found in two genotypes with distinct geographical distribution. FADs are capable of modulating the fluidity of the host’s membrane, a fundamental stress response in living cells. We show that both viral fatty acid desaturases (vFADs) families are Δ9 lipid desaturases, catalyzing the desaturation at carbon 9 in C16 fatty acid chains. In addition, we present the first fatty acid profiling for marine cyanobacteria, which suggests a unique desaturation pathway of medium to long chain fatty acids no longer than C16, in accordance to the vFADs activity. Our findings suggest that cyanophages fiddle with the infected host’s cell, leading to increased photoprotection and potentially enhancing viral-encoded photosynthetic proteins, resulting in a new viral metabolic network.

scholarly journals Structure and Function of Δ9-Fatty Acid Desaturase

2019 ◽  
Vol 67 (4) ◽  
pp. 327-332 ◽  
Author(s):  
Kohjiro Nagao ◽  
Akira Murakami ◽  
Masato Umeda
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Desaturase ◽  
Structure And Function ◽  
And Function

Saccharomyces kluyveri FAD3 encodes an ω3 fatty acid desaturase

Microbiology ◽  
2004 ◽  
Vol 150 (6) ◽  
pp. 1983-1990 ◽  
Author(s):  
Takahiro Oura ◽  
Susumu Kajiwara
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Linolenic Acid ◽  
Functional Characterization ◽  
Fatty Acid Desaturase ◽  
Fatty Acid Desaturases ◽  
Desaturase Gene ◽  
Saccharomyces Kluyveri ◽  
Fatty Acid Desaturase Gene

Fungi, like plants, are capable of producing the 18-carbon polyunsaturated fatty acids linoleic acid and α-linolenic acid. These fatty acids are synthesized by catalytic reactions of Δ12 and ω3 fatty acid desaturases. This paper describes the first cloning and functional characterization of a yeast ω3 fatty acid desaturase gene. The deduced protein encoded by the Saccharomyces kluyveri FAD3 gene (Sk-FAD3) consists of 419 amino acids, and shows 30–60 % identity with Δ12 fatty acid desaturases of several eukaryotic organisms and 29–31 % identity with ω3 fatty acid desaturases of animals and plants. During Sk-FAD3 expression in Saccharomyces cerevisiae, α-linolenic acid accumulated only when linoleic acid was added to the culture medium. The disruption of Sk-FAD3 led to the disappearance of α-linolenic acid in S. kluyveri. These findings suggest that Sk-FAD3 is the only ω3 fatty acid desaturase gene in this yeast. Furthermore, transcriptional expression of Sk-FAD3 appears to be regulated by low-temperature stress in a manner different from the other fatty acid desaturase genes in S. kluyveri.

Yeast Δ12 Fatty Acid Desaturase: Gene Cloning, Expression, and Function

2004 ◽  
Vol 68 (3) ◽  
pp. 721-727 ◽  
Author(s):  
Kyoko WATANABE ◽  
Takahiro OURA ◽  
Hiromichi SAKAI ◽  
Susumu KAJIWARA
Keyword(s):  
Fatty Acid ◽  
Gene Cloning ◽  
Fatty Acid Desaturase ◽  
Desaturase Gene ◽  
And Function ◽  
Fatty Acid Desaturase Gene

scholarly journals Linking Tumor Microenvironment to Plasticity of Cancer Stem Cells: Mechanisms and Application in Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Chune Yu ◽  
Mingqing Xu
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Immune Escape ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
And Function ◽  
The Relationship

Cancer stem cells (CSCs) are a minority subset of cancer cells that can drive tumor initiation, promote tumor progression, and induce drug resistance. CSCs are difficult to eliminate by conventional therapies and eventually mediate tumor relapse and metastasis. Moreover, recent studies have shown that CSCs display plasticity that renders them to alter their phenotype and function. Consequently, the varied phenotypes result in varied tumorigenesis, dissemination, and drug-resistance potential, thereby adding to the complexity of tumor heterogeneity and further challenging clinical management of cancers. In recent years, tumor microenvironment (TME) has become a hotspot in cancer research owing to its successful application in clinical tumor immunotherapy. Notably, emerging evidence shows that the TME is involved in regulating CSC plasticity. TME can activate stemness pathways and promote immune escape through cytokines and exosomes secreted by immune cells or stromal cells, thereby inducing non-CSCs to acquire CSC properties and increasing CSC plasticity. However, the relationship between TME and plasticity of CSCs remains poorly understood. In this review, we discuss the emerging investigations on TME and CSC plasticity to illustrate the underlying mechanisms and potential implications in suppressing cancer progression and drug resistance. We consider that this review can help develop novel therapeutic strategies by taking into account the interlink between TME and CSC plasticity.

scholarly journals Characterization and molecular docking of new Δ17 fatty acid desaturase genes from Rhizophagus irregularis and Octopus bimaculoides

RSC Advances ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 6871-6880 ◽  
Author(s):  
Chunchi Rong ◽  
Haiqin Chen ◽  
Xin Tang ◽  
Zhennan Gu ◽  
Jianxin Zhao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Molecular Docking ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Fatty Acid Desaturase ◽  
Rhizophagus Irregularis ◽  
Fatty Acid Desaturases ◽  
Key Enzymes

Fatty acid desaturases are key enzymes in the biosynthesis of n-3 polyunsaturated fatty acids (PUFAs) via conversion of n-6 polyunsaturates to their n-3 counterparts.

Substrate specificity, regioselectivity and cryptoregiochemistry of plant and animal ω-3 fatty acid desaturases

2000 ◽  
Vol 28 (6) ◽  
pp. 632-635 ◽  
Author(s):  
D. Meesapyodsuk ◽  
D. W. Reed ◽  
C. K. Savile ◽  
P. H. Buist ◽  
U. A. Schäfer ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Bond Cleavage ◽  
Isotope Effects ◽  
Fatty Acid Desaturases ◽  
Yeast Saccharomyces Cerevisiae ◽  
Kinetic Isotope ◽  
Acid Analogue ◽  
And Function

In order to define the substrate requirements, regiochemistry and cryptoregiochemistry of the ω-3 fatty acid desaturases involved in polyunsaturated fatty acid formation, the genes Fad3 and fat-1 from Brassica napus and the nematode Caenorhabditis elegans respectively were expressed in baker's yeast (Saccharomyces cerevisiae). Various fatty acids, including deuterium-labelled thia-fatty acids, were supplied to growing cultures of transformed yeast. The results from GC-MS analysis of the desaturated products indicate that both the plant and animal desaturases act on unsaturated substrates of 16–20 carbons with a preference for ω-6-unsaturated fatty acids. The regioselectivities of both enzymes were confirmed to be that of ω-3 desaturases. The primary deuterium kinetic isotope effects at C-15 and C-16 of a C18 fatty acid analogue were measured via competitive incubation experiments. Whereas kH/kD at the ω-3 position was shown to be large, essentially no kinetic isotope effect at the ω-2 position was observed for the plant or the nematode enzymes. These results indicate that ω-3 desaturation is initiated by an energetically difficult C-H bond cleavage at the carbon closer to the carboxyl terminus. These results will be discussed in the context of a general model relating the structure and function of membrane-bound fatty acid desaturases featuring different regioselectivities.

scholarly journals Homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4347 ◽  
Author(s):  
Lawal Garba ◽  
Mohamad Ariff Mohamad Yussoff ◽  
Khairul Bariyyah Abd Halim ◽  
Siti Nor Hasmah Ishak ◽  
Mohd Shukuri Mohamad Ali ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Homology Modeling ◽  
Palmitic Acid ◽  
Fatty Acid Desaturase ◽  
Three Dimensional ◽  
Docking Studies ◽  
Fatty Acid Desaturases ◽  
Protein Model ◽  
Cold Tolerant ◽  
Membrane Bound

Membrane-bound fatty acid desaturases perform oxygenated desaturation reactions to insert double bonds within fatty acyl chains in regioselective and stereoselective manners. The Δ9-fatty acid desaturase strictly creates the first double bond between C9 and 10 positions of most saturated substrates. As the three-dimensional structures of the bacterial membrane fatty acid desaturases are not available, relevant information about the enzymes are derived from their amino acid sequences, site-directed mutagenesis and domain swapping in similar membrane-bound desaturases. The cold-tolerantPseudomonassp. AMS8 was found to produce high amount of monounsaturated fatty acids at low temperature. Subsequently, an active Δ9-fatty acid desaturase was isolated and functionally expressed inEscherichia coli. In this paper we report homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8 for the first time to the best of our knowledge. Three dimensional structure of the enzyme was built using MODELLER version 9.18 using a suitable template. The protein model contained the three conserved-histidine residues typical for all membrane-bound desaturase catalytic activity. The structure was subjected to energy minimization and checked for correctness using Ramachandran plots and ERRAT, which showed a good quality model of 91.6 and 65.0%, respectively. The protein model was used to preform MD simulation and docking of palmitic acid using CHARMM36 force field in GROMACS Version 5 and Autodock tool Version 4.2, respectively. The docking simulation with the lowest binding energy, −6.8 kcal/mol had a number of residues in close contact with the docked palmitic acid namely, Ile26, Tyr95, Val179, Gly180, Pro64, Glu203, His34, His206, His71, Arg182, Thr85, Lys98 and His177. Interestingly, among the binding residues are His34, His71 and His206 from the first, second, and third conserved histidine motif, respectively, which constitute the active site of the enzyme. The results obtained are in compliance with thein vivoactivity of the Δ9-fatty acid desaturase on the membrane phospholipids.

scholarly journals Proteasomal Modulation of Cellular SNAT2 (SLC38A2) Abundance and Function by Unsaturated Fatty Acid Availability

2015 ◽  
Vol 290 (13) ◽  
pp. 8173-8184 ◽  
Author(s):  
Francesca Nardi ◽  
Thorsten M. Hoffmann ◽  
Clare Stretton ◽  
Emma Cwiklinski ◽  
Peter M. Taylor ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Unsaturated Fatty Acid ◽  
And Function
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