Acyl-CoA

About: Acyl-CoA is a research topic. Over the lifetime, 527 publications have been published within this topic receiving 25134 citations. The topic is also known as: Acyl Coenzyme A.

Acyl CoA:cholesterol acyltransferase genes and knockout mice.

Abstract: Acyl coenzyme A:cholesterol acyltransferase (ACAT) (EC 23126) is an enzyme, located in the endoplasmic reticulum of many types of cells, that catalyzes cholesterol ester formation from cholesterol and fatty acyl CoA substrates Sterol esterification by ACAT or homologous enzymes is conserved in evolution dating back to yeast The recent cloning of a human cDNA for ACAT, together with genome sequencing projects, has led to the identification of an ACAT gene family and provided molecular tools for determining ACAT's functions in vivo Summarized here is the current knowledge concerning the molecular genetics of ACAT

Fatty acyl transferase. Characterization of the enzyme as part of the yeast fatty acid synthetase complex by the use of radioactively labeled coenzyme A

Abstract: A method is described for the isolation of radioactively labeled coenzyme A from yeast which was grown on [1-14C]pantothenic acid. From about 800 g of wet cells 38 μmoles of chromatographically pure S-benzoyl-[14C]coenzyme A were obtained. It was shown that purified yeast fatty acid synthetase catalyzes a fatty acyl transfer reaction between labeled and unlabeled coenzyme A. All saturated fatty acids with chain lenghts between 6 and 18 C-atoms were transferred at about equal rates. Malonate was transferred about three times faster, acetate, propionate and butyrate about ten times slower than palmitate. Almost no transfer of crotonate and β-hydroxybutyrate was observed. The transferase was resistant to N-ethylmaleimide and iodoacetamide inhibition. It is suggested that the binding sites involved in the acyl transfer reactions are the non-thiol substrate binding sites of the fatty acid synthetase complex, and not the “central” or “peripheral” SH-groups. Both transferase and total fatty acid synthetase are inhibited by long chain fatty acyl CoA compounds. This inhibition increases with concentration and chain length of the acyl CoA derivative. It is assumed that there is a barrier for the transfer of fatty acids other than acetate from the outer transferase binding site to the active center of the fatty acid synthetase complex, and vice versa. By a local conformational change induced by the end products palmitate and stearate, bound to the “central” SH-group, this block is released to allow the acids to be transferred from the enzyme to external coenzyme A. Simultaneously, this conformational change is assumed to block further chain elongation.

Malonyl CoA, long chain fatty acyl CoA and insulin resistance in skeletal muscle.

Abstract: Malonyl CoA is an inhibitor of carnitine palmitoyl transferase 1 (CPT1), the enzyme that regulates the transfer of long chain fatty acyl CoA into mitochondria. By virtue of this effect, it is thought to play a key role in regulating fatty acid oxidation. Thus, when the supply of glucose to muscle is increased, malonyl CoA levels increase in keeping with a decreased need for fatty acid oxidation, and fatty acids are preferentially esterified to form diaglycerol and triglycerides. In contrast, during exercise, when the need for fatty acid oxidation is increased, malonyl CoA levels fall. Changes in glucose supply regulate malonyl CoA by modulating the concentration of cytosolic citrate, an allosteric activator of acetyl CoA carboxylase (ACC), the rate-limiting enzyme for malonyl CoA formation and a precursor of its substrate cytosolic acetyl CoA. Conversely, exercise lowers the concentration of malonyl CoA, by activating an AMP-activated protein kinase, which phosphorylates and inhibits ACC. A number of reports have linked sustained increases in the concentration of malonyl CoA in muscle to insulin resistance. In this paper, we review these reports, as well as the notion that changes in malonyl CoA contribute to the increases in long chain fatty acyl CoA, (LCFA CoA), diacylglycerol and triglyceride content and changes in protein kinase C activity and distribution observed in insulin-resistant muscle. We also review the implications of the malonyl CoA/LCFA CoA hypothesis to two other proposed mechanisms for insulin resistance, the glucose-fatty acid cycle and the hexosamine theory.

Enhanced triacylglycerol production in the diatom Phaeodactylum tricornutum by inactivation of a Hotdog-fold thioesterase gene using TALEN-based targeted mutagenesis

Abstract: In photosynthetic oleaginous microalgae, acyl-CoA molecules are used as substrates for the biosynthesis of membrane glycerolipids, triacylglycerol (TAG) and other acylated molecules. Acyl-CoA can also be directed to beta-oxidative catabolism. They can be utilized by a number of lipid metabolic enzymes including endogenous thioesterases, which catalyze their hydrolysis to release free fatty acids. Acyl-CoA availability thus plays fundamental roles in determining the quantity and composition of membrane lipids and storage lipids. Here, we have engineered the model diatom Phaeodactylum tricornutum to produce significantly increased TAGs by disruption of the gene encoding a Hotdog-fold thioesterase involved in acyl-CoA hydrolysis (ptTES1). This plastidial thioesterase can hydrolyze both medium- and long-chain fatty acyl-CoAs, but has the highest activity toward long-chain saturated and monounsaturated fatty acyl-CoAs. The maximum rate was found with oleoyl-CoA, which is hydrolyzed at 50 nmol/min/mg protein. The stable and targeted interruption of acyl-CoA thioesterase gene was achieved using a genome editing technique, transcription activator-like effector nucleases (TALENs). Disruption of native ptTES1 gene resulted in a 1.7-fold increase in TAG content when algal strains were grown in nitrogen-replete media for 8 days, whereas the content of other lipid classes, including phosphoglycerolipids and galactoglycerolipids, remained almost unchanged. The engineered algal strain also exhibited a marked change in fatty acid profile, including a remarkable increase in 16:0 and 16:1 and a decrease in 20:5. Nitrogen deprivation for 72 h further increased TAG content and titer of the engineered strain, reaching 478 μg/109 cells and 4.8 mg/L, respectively. Quantitative determination of in vivo acyl-CoAs showed that the total acyl-CoA pool size was significantly higher in the engineered algal strain than that in the wild type. This study supports the role of ptTES1 in free fatty acid homeostasis in the plastid of Phaeodactylum and demonstrates the potential of TALEN-based genome editing technique to generate an enhanced lipid-producing algal strain through blocking acyl-CoA catabolism.