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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In yeast, long chain acyl-CoA synthetase (ACSL) activity is required for fatty acid uptake, metabolism and fatty acid-dependent transcriptional control. The major ACSL contributing these functions is Faa1p. In a yeast two-hybrid screen, the Omi/HtrA serine protease family orthologue Ynm3p (YNL123w) was identified as a specific interactor with Faa1p. Interaction of Ynm3p and Faa1p was confirmed by co-immunoprecipitation. Disruption of the YNM3 gene encoding Ynm3p resulted in increased fatty acid uptake, triglyceride accumulation and reduced expression of the fatty acid-responsive OLE1 gene encoding the essential Delta(9)-acyl-CoA desaturase. These changes were linked with increased Faa1p and Faa4p ACSL activities. We propose that Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity. Additional strain-specific phenotypes associated with deletion of YNM3 included inability to grow on non-fermentable carbon sources and altered cellular morphology.
Mol Genet Genomics 2006 Apr
PMID:Direct interaction of Saccharomyces cerevisiae Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis. 1647 Mar 84

The double bond in anaerobic unsaturated fatty acid (UFA) biosynthesis is introduced by the FabA dehydratase/isomerase of the bacterial type II fatty acid biosynthetic pathway. A DeltafabA mutant of Pseudomonas aeruginosa grew aerobically, but required a UFA supplement for anaerobic growth. Wild-type cells produced 18:1Delta11 as the principal UFA, whereas the DeltafabA strain produced only 16:1Delta9. The double bond in the 16:1Delta9 was introduced after phospholipid formation and was localized in the sn-2 position. Two predicted membrane proteins, DesA and DesB, possessed the conserved histidine clusters characteristic of fatty acid desaturases. The DeltafabADeltadesA double mutant required exogenous fatty acids for growth but the DeltafabAdesB double mutant did not. Exogenous stearate was converted to 18:1Delta9 and supported the growth of DeltafabADeltadesA double mutant. A DeltafabADeltadesAdesB triple mutant was unable to desaturate exogenous stearate and was an UFA auxotroph. We detected a 2.5-fold increase in desA expression in DeltafabA mutants, whereas desB expression was derepressed by the deletion of the gene encoding a transcriptional repressor DesT. These data add two aerobic desaturases to the enzymes used for fatty acid metabolism in proteobacteria: DesA, a 2-position phospholipid Delta9-desaturase that supplements the anaerobic FabA pathway, and DesB, an inducible acyl-CoA Delta9-desaturase whose expression is repressed by DesT.
Mol Microbiol 2006 Apr
PMID:Two aerobic pathways for the formation of unsaturated fatty acids in Pseudomonas aeruginosa. 1657 78

Unsaturated fatty acids (UFAs) have profound effects on the fluidity and function of biological membranes. Microorganisms, plants and animals regulate the synthesis of UFAs during changing environmental conditions as well as in response to nutrients. UFAs homeostasis in many organisms is achieved by feedback regulation of fatty acid desaturase gene transcription through signalling pathways that are governed by sensors embedded in cellular membranes. Here, we review recently discovered components of the regulatory machinery governing the transcription of fatty acid desaturases in bacteria, yeasts and animals that indicate an ancient role of transmembrane signalling mechanisms and integrate membrane composition with lipid biosynthesis.
Mol Microbiol 2006 Dec
PMID:Control of fatty acid desaturation: a mechanism conserved from bacteria to humans. 1708 71

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids are currently used as an animal model for the insufficient dietary supply of such fatty acids often prevailing in Western populations. The present study deals mainly with the effects of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO), as compared to a control medium-chain triglyceride:olive oil emulsion (MCT: OO), administered as an intravenous bolus to the omega3-depleted rats 60-120 min before sacrifice upon selected biochemical and biophysical variables. The major findings consisted of a severe decrease of the omega3 fatty acid content of liver lipids in non-injected omega3-depleted rats and its partial correction after injection of the MCT:FO emulsion. The omega3-depleted rats also displayed liver steatosis, increased incorporation of long-chain polyunsaturated omega6 fatty acids in liver phospholipids and increased activity of liver Delta9-desaturase. As judged from the effects of ouabain upon 86Rb net uptake by isolated pancreatic islets, the activity of Na+,K+-ATPase was virtually abolished in the omega3-depleted rats. The latter defect was corrected by prior intravenous injection of the MCT:FO emulsion, this coinciding with suppression of the excessive secretory response to a number of insulin secretagogues otherwise observed in the islets of omega3-depleted rats injected or not with the MCT:OO emulsion.
Int J Mol Med 2006 Dec
PMID:Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride: fish oil emulsion to long-chain polyunsaturated omega3 fatty acid-depleted rats. 1708 7

Attention was recently drawn to differences in the fatty acid pattern of liver phospholipids and triglycerides in animal models of type 1 and type 2 diabetes. The present study extends this knowledge to epididymal or parametrial adipose tissue lipids. The fatty acid pattern of such lipids was established in four fed female normal rats, four overnight fasted female normal rats, six fed female rats rendered diabetic by an injection of streptozotocin 3 days before sacrifice (STZ rats), and four female and four male Goto-Kakizaki rats (GK rats) also examined in the fed or fasted state. In addition to the fasting-induced and diabetes-related changes in plasma D-glucose and insulin concentrations, differences in either the weight percentage of fatty acids or the paired ratio between distinct fatty acids were often encountered. For instance, in the GK rats, gender differences were observed in the weight percentage of C18:2omega6, as well as C18:2omega6/C18:3omega6, C18:3omega6/C20:4omega6, C20:5omega3/C22:5omega3 and C22:5omega3/C22:6omega3 ratios. When compared to normal rats, the activity of Delta9-desaturase was markedly increased in GK rats and, to a lesser extent, in STZ rats. Starvation also increased to some extent the activity of Delta9-desaturase. The relative content of C22:6omega3 was also higher in diabetic than in normal rats. Further differences between GK and STZ rats concerned the generation of C18:3omega6 from C18:2omega6, C20:4omega6 from C18:3omega6, and C20:5omega3 from C18:3omega3. Several differences found in the adipose tissue of GK versus STZ rats were reminiscent of those recently identified in the liver triglycerides of these two types of diabetic animals, suggesting a common regulatory mechanism, possibly linked to the higher insulinemia of GK rats versus STZ rats.
Int J Mol Med 2006 Dec
PMID:Fatty acid content and pattern of epididymal and parametrial adipose tissue lipids in streptozotocin (type 1) and Goto-Kakizaki (type 2) diabetic rats. 1708 31

Small interfering RNA (siRNA) species with 21-25 nucleotides in length guide mRNA cleavage, translational arrest, and heterochromatin formation in RNA interference (RNAi). To delineate the target region of RNAi, a construct harboring a transcriptional fusion between parts of the target mRNA and the beta-glucuronidase gene was biolistically delivered into tobacco leaves showing an RNAi phenotype and the assay sequence was transiently expressed. The RNAi effect was monitored by amplification of this chimeric transcript. By using this assay method, we addressed the transitive RNA silencing of a tobacco endoplasmic reticulum omega-3 fatty acid desaturase gene (NtFAD3). In the NtFAD3 RNAi plants, the target region of RNAi was restricted in the inducer region corresponding to a stem sequence of the hairpin double-stranded RNA, indicating that endogenous NtFAD3 mRNA was not a template for an RNA-dependent RNA polymerase. The secondary NtFAD3 siRNAs were produced in the crossbred plants between the NtFAD3 overexpressed plant and the NtFAD3 RNAi plant. Similarly, the secondary siRNAs were generated in the systemically silenced scion. Although these secondary siRNAs originated preferentially from the 3' region downstream of the inducer region, the secondary siRNAs produced in the silenced scion (non-cell autonomous secondary siRNAs) resulted in the strong degradation of the target mRNA, but the secondary siRNAs in the crossbred plants (cell-autonomous secondary siRNAs) showed limited RNA degradation activity. These results showed that this in vivo assay for determination of RNAi efficiency is a useful tool to delineate RNAi mechanisms.
Plant Mol Biol 2007 Apr
PMID:Generation of secondary small interfering RNA in cell-autonomous and non-cell autonomous RNA silencing in tobacco. 1722 52

The fatty acid pattern of spleen phospholipids and triglycerides was examined in fed or overnight fasted normal rats, streptozotocin-induced diabetic animals (type-1 diabetes) and Goto-Kakizaki rats (type-2 diabetes). In both phospholipids and triglycerides, differences were observed in the relative contribution of several fatty acids, as well as in the ratio between distinct fatty acids, when comparing fed to fasted rats, normal to diabetic animals and male to female Goto-Kakizaki rats. Diabetes increased to a greater extent the C22:6omega3 content of phospholipids in the spleen than in either the liver or the brain. However, the diabetes-induced changes in the C22:6omega3 content of triglycerides was closely comparable in the spleen, liver and brain. These findings suggest that the incorporation of fatty acids into triglycerides is controlled by comparable regulatory factor(s), e.g. insulinemia, in the spleen, liver and brain. In the case of phospholipids, however, an apparent adaptation to diabetic stress was more marked in the spleen than in the liver, and virtually absent in the brain. The proposed dichotomy in the environmental regulation of fatty acid synthesis and incorporation into phospholipids and triglycerides was further supported by distinct diabetes-related changes in the apparent activity of Delta9-desaturase in these two classes of lipids.
Int J Mol Med 2007 Mar
PMID:Fatty acid content and pattern of spleen phospholipids and triglycerides in normal and either type-1 or type-2 diabetic rats. 1727 3

Cells regulate their membrane phospholipid biophysical properties by the co-ordinated synthesis of saturated and unsaturated fatty acids. In bacteria, unsaturated fatty acids are produced by the de novo fatty acid biosynthetic pathway anaerobically, or by oxidative desaturation of the existing fatty acids catalysed by desaturases. A transcriptional repressor in Pseudomonas aeruginosa, DesT (PA4890), regulates the expression of an acyl-CoA desaturase operon (desCB, PA4889 and PA4888). The desCB operon is located adjacent to desT and is transcribed in the opposite direction. The expression level of desCB is strongly and selectively upregulated in a DeltadesT-deletion strain. Both electrophoresis mobility shift assay and DNase I footprinting analysis demonstrated the existence of two DesT binding sites in the desT-desCB promoter region, P1 and P2. The binding of purified DesT to P2 was enhanced by unsaturated acyl-CoAs, whereas saturated acyl-CoAs prevented DesT interaction with P2. The biological importance of this interaction was verified by the upregulation of desCB and desT in cells grown in the presence of stearate and their repression when oleate was present. This unique ligand selectivity allows DesT to sense the physical properties of the cellular acyl-CoA pool and modulate the expression of the acyl-CoA Delta9-desaturase system to adjust fatty acid desaturation activity accordingly.
Mol Microbiol 2007 Nov
PMID:A Pseudomonas aeruginosa transcription factor that senses fatty acid structure. 1787 13

Cold-acclimated non-diapause pupae, and summer- and winter-diapause pupae of the onion maggot, Delia antiqua (Diptera: Anthomyiidae), show marked cold hardiness as compared with intact non-diapause pupae. Homeoviscous adaptation of cellular membranes is crucial to enhance the cold hardiness of organisms, and Delta9-acyl-CoA desaturases have been assumed, albeit without experimental evidence in insects, to play a key role in the adaptation. We cloned the cDNA of a desaturase gene (Dadesat) from D. antiqua, which is most likely to encode Delta9-acyl-CoA desaturase. Expression of Dadesat mRNA in the brain, midgut, and Malpighian tubules of cold-acclimated and diapause pupae was upregulated 2-10 fold, correlating well with the increase in cold hardiness. In the pupae with enhanced cold hardiness, palmitoleic and oleic acids, the presumed products of Dadesat, in the phospholipids were significantly increased. These findings suggest that the increase in the expression of Dadesat contributes to enhanced cold hardiness in D. antiqua through the production of these unsaturated fatty acids.
Insect Biochem Mol Biol 2007 Nov
PMID:Upregulation of a desaturase is associated with the enhancement of cold hardiness in the onion maggot, Delia antiqua. 1791 2

We used whole genome scan association mapping to identify loci with major effect on oleic acid content in maize kernels. Single nucleotide polymorphism haplotypes at 8,590 loci were tested for association with oleic acid content in 553 maize inbreds. A single locus with major effect on oleic acid was mapped between 380 and 384 cM in the IBM2 neighbors genetic map on chromosome 4 and confirmed in a biparental population. A fatty acid desaturase, fad2, identified approximately 2 kb from the associated genetic marker, is the most likely candidate gene responsible for the differences in the phenotype. The fad2 alleles with high- and low-oleic acid content were sequenced and allelic differences in fad2 RNA level in developing embryos was investigated. We propose that a non-conservative amino acid polymorphism near the active site of fad2 contributes to the effect on oleic acid content. This is the first report of the use of a high resolution whole genome scan association mapping where a putative gene responsible for a quantitative trait was identified in plants.
Mol Genet Genomics 2008 Jan
PMID:Whole genome scan detects an allelic variant of fad2 associated with increased oleic acid levels in maize. 1793 60


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