Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: CAS:1763-10-6 (palmitoyl-CoA)
 1,624 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After incubating isolated rat hepatocytes with [1-14 C]palmitic acid, CoA and ATP (+MgCl2), a significant amount of [1-14 C]palmitoyl-CoA was found in the incubation medium. There was no correlation between its rate of synthesis and the degree of intactness of the cells. The results indicate that there is a long-chain fatty acyl-CoA synthetase active on the external surface of the hepatocyte plasma membrane. The activity of this enzyme was negligible in primary cultures of rat hepatocytes, suggesting that the exofacial long-chain acyl-CoA synthetase is an artifact of the collagenase perfusion technique used to prepare the hepatocytes.
 ...
PMID:Palmitoyl-CoA synthetase on the external surface of isolated rat hepatocytes. 895 46

The ability of Bordetella heat-labile toxin (HLT) to induce ischemic lesions after intracutaneous injection to guinea pig skin was lost following incubation at 37 degrees C with long-chain saturated acyl-CoA and acyl-carnitine compounds. Short-chain unsaturated acyl-CoA compounds, however, were less potent in inhibiting the induction of HLT activity. Long-chain saturated acyl-CoA and acyl-carnitine compounds, potently inhibited the induction of this activity. On incubation with HLT at 0 degrees C, a long-chain saturated acyl-CoA compound, palmitoyl-CoA, did not inhibit HLT activity. When first mixed with bovine serum albumin or dimethyl-beta-cyclodextrin, palmitoyl-CoA lost the ability to inhibit HLT activity. Binding of 14C-palmitoyl-CoA to HLT was measured by Scatchard analysis. The Bmax values of HLT (2.75 mol/mol of protein) were higher than that of acyl-CoA-binding protein from bovine liver (0.95 mol/mol of protein). Neither acyl-CoA hydrolase nor acyl-CoA ligase was detected in the HLT preparation. These results suggest that the acyl-CoA and acyl-carnitine compounds bind directly to HLT and produce a critical change in conformation required for HLT activity.
 ...
PMID:Inhibitory effect of acyl-CoA and acyl-carnitine compounds on the ischemia-inducing activity of Bordetella heat-labile toxin in guinea pig skin. 905 85

The trafficking of acyl-CoAs within cells is poorly understood. In order to determine whether newly synthesized acyl-CoAs are equally available for the synthesis of all glycerolipids and cholesterol esters, we incubated human fibroblasts with [14C]oleate, [3H]arachidonate or [3H]glycerol in the presence or absence of triacsin C, a fungal metabolite that is a competitive inhibitor of acyl-CoA synthetase. Triacsin C inhibited de novo synthesis from glycerol of triacylglycerol, diacylglycerol and cholesterol esters by more than 93%, and the synthesis of phospholipid by 83%. However, the incorporation of oleate or arachidonate into phospholipids appeared to be relatively unimpaired when triacsin was present. Diacylglycerol acyltransferase and lysophosphatidylcholine acyltransferase had similar dependences on palmitoyl-CoA in both liver and fibroblasts; thus it did not appear that acyl-CoAs, when present at low concentrations, would be preferentially used to acylate lysophospholipids. We interpret these data to mean that, when fatty acid is not limiting, triacsin blocks the acylation of glycerol 3-phosphate and diacylglycerol, but not the reacylation of lysophospholipids. Two explanations are possible: (1) different acyl-CoA synthetases exist that vary in their sensitivity to triacsin; (2) an independent mechanism channels acyl-CoA towards phospholipid synthesis when little acyl-CoA is available. In either case, the acyl-CoAs available to acylate cholesterol, glycerol 3-phosphate, lysophosphatidic acid and diacylglycerol and those acyl-CoAs that are used by lysophospholipid acyltransferases and by ceramide N-acyltransferase must reside in two non-mixing acyl-CoA pools or, when acyl-CoAs are limiting, they must be selectively channelled towards specific acyltransferase reactions.
 ...
PMID:Triacsin C blocks de novo synthesis of glycerolipids and cholesterol esters but not recycling of fatty acid into phospholipid: evidence for functionally separate pools of acyl-CoA. 918 14

The non-mitochondrial Ca2+ stores in permeabilized A7r5 cells responded to a decrease in Mg-ATP concentration with a pronounced Ca2+ release if 20 microM CoA was present. This release was rather specific for the preincubation or removal of ATP. ATP gamma S was much less effective and AMP-PNP, GTP, ITP, CTP, UTP, ADP, AMP, adenosine and adenine had no effect. CoA activated with an EC50 of 6 microM. Dephospho-CoA was a less effective cofactor and desulfo-CoA was ineffective. The release induced by Mg-ATP removal did not occur in the presence of 2% fatty acid-free bovine serum albumin and did not develop at 4 degrees C. All these findings suggest that CoA had to be acylated by endogenous fatty-acyl-CoA synthetase to become effective. Myristoyl- and palmitoyl-CoA esters were identified as the most effective cofactors for the release. Ca2+ release induced by removing Mg-ATP did not occur if the osmolality of the medium was kept constant by addition of mannitol, sucrose, KCl, MgCl2 or Mg-GTP, indicating that the decrease in tonicity was the trigger for the release. Mg-ATP plus CoA also synergized with Ca2+ release induced by a hypotonic shock imposed by diluting the medium with H2O. Osmolality changes induced by decreasing the Mg-ATP concentration were more effective in releasing Ca2+ than equal decreases in concentration of all solutes. We conclude that fatty acyl-CoA esters sensitize the hypotonically induced Ca2+ release from the non-mitochondrial Ca2+ stores.
 ...
PMID:Synergism between hypotonically induced calcium release and fatty acyl-CoA esters induced calcium release from intracellular stores. 933 Jul 85

In this work, an attempt was made to identify the reasons of impaired long-chain fatty acid utilization that was previously described in volume-overloaded rat hearts. The most significant data are the following: (1) The slowing down of long-chain fatty acid oxidation in severely hypertrophied hearts cannot be related to a feedback inhibition of carnitine palmitoyltransferase I from an excessive stimulation of glucose oxidation since, because of decreased tissue levels of L-carnitine, glucose oxidation also declines in volume-overloaded hearts. (2) While, in control hearts, the estimated intracellular concentrations of free carnitine are in the range of the respective Km of mitochondrial CPT I, a kinetic limitation of this enzyme could occur in hypertrophied hearts due to a 40% decrease in free carnitine. (3) The impaired palmitate oxidation persists upon the isolation of the mitochondria from these hearts even in presence of saturating concentrations of L-carnitine. In contrast, the rates of the conversion of both palmitoyl-CoA and palmitoylcarnitine into acetyl-CoA are unchanged. (4) The kinetic analyses of palmitoyl-CoA synthase and carnitine palmitoyltransferase I reactions do not reveal any differences between the two mitochondrial populations studied. On the other hand, the conversion of palmitate into palmitoylcarnitine proves to be substrate inhibited already at physiological concentrations of exogenous palmitate. The data presented in this work demonstrate that, during the development of severe cardiac hypertrophy, a fragilization of the mitochondrial outer membrane may occur. The functional integrity of this membrane seems to be further deteriorated by increasing concentrations of free fatty acids which gives rise to an impaired cooperation between palmitoyl-CoA synthase and carnitine palmitoyltransferase I. In intact myocardium, the utilization of the in situ generated palmitoyl-CoA can be further slowed down by decreased intracellular concentrations of free carnitine.
 ...
PMID:Palmitate oxidation by the mitochondria from volume-overloaded rat hearts. 954 38

Biopharmacological evaluations of the protective effects of L-carnitine (a naturally occurring quaternary ammonium compound) against doxorubicin-induced metabolic damage were carried out in isolated cardiac myocytes and in isolated rat heart mitochondria. Perfusion of the heart with DOX (0.5 mM) caused a significant 70% inhibition of palmitate oxidation in cardiac myocytes, while L-carnitine (5 mM) perfusion caused stimulation which accounted for 37%. Perfusion of the heart with L-carnitine after 10-min perfusion with DOX (0.5 mM) caused 88% reversal of DOX-induced inhibition of palmitate oxidation in cardiac cells. In rat heart mitochondria, DOX has no effect on either palmitate oxidation or acyl-CoA synthetase activity, whereas Enoximone (c-AMP-dependent phosphodiesterase inhibitor), caused a significant inhibition of palmitate oxidation and acyl-CoA activity (40 and 27%, respectively). The oxidation of palmitoyl-CoA, an index of carnitine palmitoyltransferse reaction was significantly inhibited by DOX as a function of DOX concentration. Preincubation of mitochondria with L-carnitine caused reversal of DOX-induced inhibition of palmitoyl-CoA oxidation depending on the concentration of L-carnitine. Moreover, L-carnitine treatment did not interfere with the cytotoxic effect of doxorubicin against the growth of solid Ehrlich carcinoma. The findings of this study may suggest that inhibition of fatty acid oxidation in the heart is at least a part of doxorubicin cardiotoxicity and that L-carnitine can be used to prevent the doxorubcin-induced cardiac metabolic damage without interfering with its antitumour activities.
 ...
PMID:Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine. 1020 59

Recently, it has become clear that the peroxisomal beta-oxidation system in rat and man consists of multiple pathways. In rat and man straight chain fatty acids, dicarboxylic fatty acids and prostaglandins are oxidized via the L-specific pathway catalyzed by palmitoyl-CoA oxidase, multifunctional protein-1 and thiolase. 2-Methyl-branched fatty acids and the bile acid intermediates are oxidized via the D-specific pathway. In the rat this pathway is catalyzed by prostanoyl-CoA oxidase, multifunctional protein-2 and sterol carrier protein-X (branched fatty acids) and by trihydroxycoprostanoyl-CoA oxidase, multifunctional protein-2 and sterol carrier protein-X (bile acid intermediates). In the human, branched fatty acids and bile acid intermediates are oxidized via branched chain acyl-CoA oxidase, multifunctional protein-2 and sterol carrier protein-X. All enzymes of these pathways have been purified, cloned and characterized. Also the reactions that constitute the alpha-oxidation pathway for 3-methyl-branched fatty acids, have recently been identified in rat and man. The revised pathway consists of the following reactions: 1) an activation reaction catalyzed by an acyl-CoA synthetase, that forms a 3-methylacyl-CoA; 2) a hydroxylation (dioxygenase) reaction catalyzed by a 3-methylacyl-CoA 2-hydroxylase, that converts the CoA ester to a 2-hydroxy-3-methylacyl-CoA; 3) a cleavage reaction catalyzed by a 2-hydroxy-3-methylacyl-CoA lyase, that releases a 2-methyl fatty aldehyde and formyl-CoA. The branched aldehyde is dehydrogenated by an aldehyde dehydrogenase to a 2-methyl branched fatty acid that can be degraded by peroxisomal beta-oxidation. Formyl-CoA is enzymatically hydrolyzed to formate which is then converted to CO2.
 ...
PMID:[Lipid degradation by way of beta and alpha oxidation in peroxisomes of mammals]. 1037 98

The primary sequence of the murine fatty acid transport protein (FATP1) is very similar to the multigene family of very long chain (C20-C26) acyl-CoA synthetases. To determine if FATP1 is a long chain acyl coenzyme A synthetase, FATP1-Myc/His fusion protein was expressed in COS1 cells, and its enzymatic activity was analyzed. In addition, mutations were generated in two domains conserved in acyl-CoA synthetases: a 6- amino acid substitution into the putative active site (amino acids 249-254) generating mutant M1 and a 59-amino acid deletion into a conserved C-terminal domain (amino acids 464-523) generating mutant M2. Immunolocalization revealed that the FATP1-Myc/His forms were distributed between the COS1 cell plasma membrane and intracellular membranes. COS1 cells expressing wild type FATP1-Myc/His exhibited a 3-fold increase in the ratio of lignoceroyl-CoA synthetase activity (C24:0) to palmitoyl-CoA synthetase activity (C16:0), characteristic of very long chain acyl-CoA synthetases, whereas both mutant M1 and M2 were catalytically inactive. Detergent-solubilized FATP1-Myc/His was partially purified using nickel-based affinity chromatography and demonstrated a 10-fold increase in very long chain acyl-CoA specific activity (C24:0/C16:0). These results indicate that FATP1 is a very long chain acyl-CoA synthetase and suggest that a potential mechanism for facilitating mammalian fatty acid uptake is via esterification coupled influx.
 ...
PMID:The fatty acid transport protein (FATP1) is a very long chain acyl-CoA synthetase. 1059 20

(i) Highly purified mitochondrial fractions were practically devoid of microsomal contamination and of acyl-CoA ligase activity. (ii) In mitochondria, glycerol-3-phosphate acyltransferase (GPAT) activity was supported by two enzymes, the first being very active at low palmitoyl-CoA/albumin ratios and sensitive to external agents (external form), the second being detected only at higher palmitoyl-CoA/albumin ratios and insensitive to external agents (internal form). (iii) Carnitine palmitoyltransferase I (CPT I) activity was shown to inhibit external GPAT activity only. (iv) Glycerol-3-phosphate exerted an inhibitory effect on CPT I, even when GPAT was inactive. Reciprocal interaction of CPT I and GPAT was discussed with regard to the balance existing between fatty acid oxidation and esterification metabolic pathways.
 ...
PMID:Reciprocal enzymatic interference of carnitine palmitoyltransferase I and glycerol-3-phosphate acyltransferase in purified liver mitochondria. 1070 29

Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). In the present study, we investigated the effects of palmitic acid (PA) and palmitoyl-CoA (PA-CoA) on the PG and AA-CoA formation from high and low concentrations of AA (60 and 5 microM) in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 60 or 5 microM [14C]-AA in 0.1 M-Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl2 and CoA). After incubation, PG (as total PGs), AA-CoA and residual AA were separated by selective extraction using petroleum ether and ethyl acetate. PA (10-100 microM) had no effect on the PG and AA-CoA formation from either 60 or 5 microM AA. PA-CoA (10-100 microM) was without effect on the PG and AA-CoA formation from 60 microM AA, whereas it markedly decreased the PG formation (6-40%) and increased the AA-CoA formation (1.1-2.3-fold) from 5 microM AA, showing that the effects of PA-CoA on the PG and AA-CoA formation change depending on the AA concentration. These results suggest that PA-CoA, but not PA, may regulate the PG and AA-CoA formation at low substrate concentrations (close to the physiological concentration of AA), and that this in-vitro method using 5 microM AA may be useful for clarifying the homeostatic control of the metabolic fate of AA into these two enzymatic pathways.
 ...
PMID:The regulation of prostaglandin and arachidonoyl-CoA formation from arachidonic acid in rabbit kidney medulla microsomes by palmitoyl-CoA. 1073 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>