Showing papers on "Acyl-CoA published in 2007"
TL;DR: Saccharomyces cerevisiae forms monounsaturated fatty acids using the ER membrane-bound Delta-9 fatty acid desaturase, Ole1p, an enzyme system that forms a double bond in saturated fatty acyl CoA substrates.
209 citations
TL;DR: Gain- and loss-of-function studies show marked differences in the ability of these enzymes to channel fatty acids into different pathways of complex lipid synthesis.
Abstract: Thirteen homologous proteins comprise the long-chain acyl-CoA synthetase (ACSL), fatty acid transport protein (FATP), and bubblegum (ACSBG) subfamilies that activate long-chain and very-long-chain fatty acids to form acyl-CoAs. Gain- and loss-of-function studies show marked differences in the ability of these enzymes to channel fatty acids into different pathways of complex lipid synthesis. Furthermore, the ability of the ACSLs and FATPs to enhance cellular FA uptake does not always require these proteins to be present on the plasma membrane; instead, fatty acid uptake can be increased by enhancing its conversion to acyl-CoA and its metabolism in downstream pathways. Since altered fatty acid metabolism is a hallmark of numerous metabolic diseases and pathological conditions, the ACSL, FATP and ACSBG isoforms are likely to play important roles in disease etiology.
206 citations
TL;DR: Evidence from directed experimentation, as well as information obtained by mining the molecular biological databases suggesting the long chain ACS enzymes are required in protein acylation, vesicular trafficking, signal transduction pathways and cell wall synthesis are presented.
191 citations
TL;DR: The levels of very-long-chain fatty acids, long-chain bases and ceramide are severely affected by Acb1p depletion, suggesting that Acb 1p, rather than playing a general role, serves specific roles in cellular lipid metabolism.
Abstract: Besides serving as essential substrates for β-oxidation and synthesis of triacylglycerols and more complex lipids like sphingolipids and sterol esters, long-chain fatty acyl-CoA esters are increasingly being recognized as important regulators of enzyme activities and gene transcription. Acyl-CoA binding protein, ACBP, has been proposed to play a pivotal role in the intracellular trafficking and utilization of long-chain fatty acyl-CoA esters. Depletion of acyl-CoA binding protein in yeast results in aberrant organelle morphology incl. fragmented vacuoles, multi-layered plasma membranes and accumulation of vesicles of variable sizes. In contrast to synthesis and turn-over of glycerolipids, the levels of very-long-chain fatty acids, long-chain bases and ceramide are severely affected by Acb1p depletion, suggesting that Acb1p, rather than playing a general role, serves specific roles in cellular lipid metabolism.
80 citations
TL;DR: PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
Abstract: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
44 citations
TL;DR: Recombinantly expressed ACNAT1 acts as an acyltransferase that efficiently conjugates very long‐ chain and long‐chain fatty acids to taurine, identifying a novel pathway for production of N‐acyltaurines as signaling molecules or for excretion of fatty acids in peroxisomes.
Abstract: A wide variety of endogenous carboxylic acids and xenobiotics are conjugated with amino acids, before excretion in urine or bile. The conjugation of carboxylic acids and bile acids with taurine and...
42 citations
TL;DR: The transcriptome pattern of metabolic genes in vitamin A deficient (VAD) liver has been compared to the vitamin A-sufficient (VAS) state and found an increase in hepatic macrocytic lipid accumulation and triglyceride levels.
35 citations
TL;DR: This issue describes the reconstitution of this multienzyme complex in liposomes and reveals how elongase proteins (Elops) determine the final length of the fatty acyl CoA chain.
30 citations
TL;DR: Investigating work revealed that LDL uptake and fatty acid oxidation were not involved in the I-3-C-mediated reduction of apoB secretion, indicating that plant indoles have beneficial effects on lipid synthesis that could contribute to their potential cardioprotective effect.
Abstract: The cardioprotective effect of consuming cruciferous vegetables may be attributed to a number of unique indole-based compounds. We investigated the potential role and mechanism of action of an indole-based compound, indole-3-carbinol (I-3-C), on apolipoprotein B-100 (apoB) production using HepG2 cells. I-3-C reduced apoB secretion into the media dose dependently by 56% at 100 micromol/L. Relative to the untreated control cells, no change in the density of the secreted lipoproteins was noted. Significant decreases in cellular lipid synthesis, including triglycerides (TG) and cholesterol esters (CE), were observed in cells treated with I-3-C, indicating that limited lipid availability is a major factor in the regulation of apoB secretion. The decrease in TG synthesis was associated with significantly decreased diacylglycerol acyltransferase-1 and -2 activity and reduced fatty acid synthase (FASN) gene expression. The decreased CE synthesis was associated with significantly decreased acyl CoA:cholesterol acyltransferase gene expression and activity. The effect on FASN was shown to be mediated by sterol regulatory element binding protein-1, an important transcription factor involved in fatty acid synthesis. Further investigative work revealed that LDL uptake and fatty acid oxidation were not involved in the I-3-C-mediated reduction of apoB secretion. The results indicate that plant indoles have beneficial effects on lipid synthesis that could contribute to their potential cardioprotective effect.
28 citations
TL;DR: Data show that the Acot7 gene is expressed as multiple isoforms in a tissue-specific manner, and that expression in tissues other than brain and testis is likely to play important roles in fatty acid metabolism.
Abstract: Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues. In this study, we have identified five possible first exons in mouse Acot7 (Acot7a-e) and show that all five first exons are transcribed in a tissue-specific manner. Taken together, these data show that the Acot7 gene is expressed as multiple isoforms in a tissue-specific manner, and that expression in tissues other than brain and testis is likely to play important roles in fatty acid metabolism.
22 citations
TL;DR: One isoprenyl flavonoid was isolated from ethanol extract of licorice roots and showed a non-competitive type of inhibition against ACAT, which may act as antihypercholesterolemic and antiatherosclerotic agents.
Dissertation•
18 May 2007
TL;DR: This PhD project began with the identification of four novel putative peroxisomal acyl-CoA thioesterase genes, named ACOT3-Acot6, and revealed that expression of all four enzymes is upregulated byPeroxisome proliferator activated receptor α (PPARα) dependent manner, suggesting that they function in fatty acid metabolism.
Abstract: Peroxisomes are small organelles essential for life, which carry out a variety of functions mostly related to lipid metabolism, including αand β-oxidation as well as the first steps of plasmalogen biosynthesis. Peroxisomal β-oxidation metabolizes many different lipids including very long-chain fatty acids, dicarboxylic fatty acids, branched-chain fatty acids, eicosanoids and certain xenobiotic fatty acids. This PhD project began with the identification of four novel putative peroxisomal acylCoA thioesterase genes, named acyl-CoA thioesterase 3-6 (Acot3-Acot6). The acylCoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. The identification of these novel acyl-CoA thioesterases raised questions as to their function(s) and what the need is for so many peroxisomal acyl-CoA thioesterases. Answering these questions was therefore the aim of this project. Biochemical characterization showed that expression of all four enzymes is upregulated by peroxisome proliferators in a peroxisome proliferatoractivated receptor α (PPARα) dependent manner, suggesting that they function in fatty acid metabolism. Further characterization revealed that ACOT3 and ACOT5 are a longand a medium-chain acyl-CoA thioesterase, respectively, while ACOT4 and ACOT6 were shown to be specific enzymes catalyzing the hydrolysis of succinyl-CoA and phytanoyl-CoA/pristanoyl-CoA, respectively. ACOT3-ACOT6 were also shown to have distinct tissue expression patterns, suggesting that these enzymes carry out specific functions in different tissues. The peroxisomal acyl-CoA thioesterases not only have the potential to terminate oxidation by hydrolysis of the acyl-CoAs, but the free fatty acids produced may also be able to exit peroxisomes, suggesting a function for these enzymes in transport of fatty acids out of peroxisomes. A wide variety of lipids are oxidized in peroxisomes producing a diversity of products that require to exit peroxisomes, which demonstrates the need for multiple acyl-CoA thioesterase activities in peroxisomal lipid metabolism. LIST OF PUBLICATIONS I. Westin, M. A. K., Alexson, S. E. H., and Hunt, M. C. Molecular cloning and characterization of two mouse peroxisome proliferator activated receptor α (PPARα) -regulated peroxisomal acyl-CoA thioesterases J. Biol. Chem. (2004) 279 (21): 21841-21848 II. Westin, M. A. K., Alexson, S. E. H., and Hunt, M. C. The identification of a succinyl-CoA thioesterase suggests a novel pathway for succinate production in peroxisomes J. Biol. Chem. (2005) 280 (46): 38125-38132 III. Westin, M. A. K., Hunt, M. C., and Alexson, S. E. H. Peroxisomes contain a specific phytanoyl-CoA/pristanoyl-CoA thioesterase acting as a novel auxiliary enzyme in alphaand beta-oxidation of methylbranched fatty acids Submitted IV. Westin, M. A. K., Hunt, M. C., and Alexson, S. E. H. Tissue expression studies of enzymes involved in peroxisomal lipid metabolismnew insights into the functions of acyl-CoA thioesterases and carnitine acyltransferases Submitted Related work: Hunt, M. C., Rautanen, A., Westin, M. A. K., Svensson, L. T., and Alexson, S. E. H. Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs FASEB J. (2006) 20: 1855-1864