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

1. Long-chain acid: CoA ligase (AMP-forming) (trivial name acyl-CoA synthetase; EC 6.2.1.3) is located at the membranes of the endoplasmic reticulum and the outer membrane of the mitochondria. The latter membrane has by far the highest specific activity. 2. GTP-dependent synthesis of acyl-CoA has a very low activity in liver mitochondria (about 5% of the activity measured with ATP). CTP, ITP, UTP and GTP may all provide energy for fatty acid activation in sonicated mitochondria by formation of ATP from endogenous ADP and AMP. 3. In rat liver palmitoyl-CoA: L-carnitine O-palmitoyltransferase (trivial name carnitine palmitoyltransferase; EC 2.3.1.21) is located at the microsomal membranes and in the inner membrane of the mitochondria. Its activity is increased, in both membranes, during fasting and in thyroxine-treated rats. The extramitochondrial carnitine palmitoyltransferase may capture part of the acyl CoA formed at the endoplasmic reticulum as acyl-carnitine, especially during fasting and other metabolic conditions of high fatty acid turnover. This transport form of activated fatty acid can penetrate the inner mitochondrial membrane (the acyl-CoA barrier) where it can be reconverted to acyl-CoA, providing the substrate for beta-oxidation in the inner membrane-matrix compartment. The small part of the mitochondrial carnitine palmitoyltransferase, described to be present at the external surface of the mitochondrial inner membrane, may have the same function in the transport of acyl-CoA formed at the mitochondrial outer membrane. 4. Isolated rat liver mitochondria can oxidize high concentrations of palmitate or oleate in the absence of carnitine. In this case the fatty acids are activated in the inner membrane-matrix compartment of the mitochondria, probably by a medium-chain acyl-CoA synthetase with wide substrate specificity. Because this enzyme is less active in heart and absent in skeletal muscle, these tissues oxidize long-chain fatty acids in an obligatory carnitine-dependent fashion. Also the liver oxidizes long-chain fatty acids in a carnitine-dependent way if lower fatty acid concentrations are used. In this tissue carnitine stimulates specifically the partial oxidation of fatty acids to beta-hydroxybutyrate and acetoacetate. 5. The activities of acyl-CoA: sn-glycerol-3-phosphate O-acyltransferase (trivial name glycerophosphate acyltransferase; EC 2.3.1.15) and carnitine palmitoyltransferase change in opposite directions during fasting. These activity changes, together with the measured kinetic properties of the enzymes in mitochondria and microsomes, allow a switch (relatively) from lipid synthesis to ketogenesis during fasting. This switch may occur at the level of long-chain acyl-CoA both in the endoplasmic reticulum and in the mitochondria.
Mol Cell Biochem 1975 Apr 30
PMID:Aspects of long-chain acyl-COA metabolism. 113 97

The alkBFGHJKL and alkST operons encode enzymes that allow Pseudomonas putida (oleovorans) to metabolize alkanes. In this paper we report the nucleotide sequence of a 4592 bp region of the alkBFGHJKL operon encoding the AlkJ, AlkK and AlkL polypeptides. The alkJ gene encodes a protein of 59 kilodaltons. The predicted amino acid sequence shows significant homology with four flavin proteins: choline dehydrogenase, a glucose dehydrogenase and two oxidases. AlkJ is membrane-bound and converts aliphatic medium-chain-length alcohols into aldehydes. The properties of AlkJ suggest that it is linked to the electron transfer chain. AlkJ is necessary for growth on alkanes only in P. putida alcohol dehydrogenase (AlcA) mutants. AlkK is homologous to a range of proteins which act by an ATP-dependent covalent binding of AMP to their substrate. This list includes the acetate, coumarate and long-chain fatty acid CoA ligases. The alkK gene complements a fadD mutation in Escherichia coli, which shows that it indeed encodes an acyl-CoA synthetase. AlkK is a 60 kilodalton protein located in the cytoplasm. AlkL is homologous to OmpW, a Vibrio cholerae outer membrane protein of unknown function, and a hypothetical polypeptide encoded by ytt4 in E. coli. AlkL, OmpW and Ytt4 all have a signal peptide and end with a sequence characteristic of outer membrane proteins. The alkL gene product was found in the outer membrane of E. coli W3110 containing the alk-genes. The alkL gene can be deleted without a clear effect on growth rate. Its function remains unknown. The G+C content of the alkJKL genes is 45%, identical to that of the alkBFGH genes, and significantly lower than the G+C content of the OCT-plasmid and the P. putida chromosome.
Mol Microbiol 1992 Nov
PMID:DNA sequence determination and functional characterization of the OCT-plasmid-encoded alkJKL genes of Pseudomonas oleovorans. 145 53

Studies carried out on the adrenal glands of experimental diabetic rats have shown an important inhibition in polyenoic fatty acid biosynthesis. This effect was demonstrated by testing the activities of long-chain fatty acyl-CoA synthetase, the delta 5- and delta 6-desaturases of the (n-6) essential fatty-acid series and the delta 6-desaturase of the (n-3) series in liver and adrenal microsomes. The depression in desaturating activity in the insulin-deprived animals was independent of that produced on acyl-CoA-thioester biosynthesis. Experiments measuring the incorporation and transformation of [1-14C]eicosa-8,11,14-trienoic acid in adrenocortical cells isolated from streptozotocin-diabetic animals demonstrated a significant inhibition of arachidonic acid biosynthesis compared to controls. Insulin injections in diabetic rats partially restored the delta 5- and delta 6-desaturase activities. This effect could result from direct action by the hormone since the restoration was reproduced when arachidonic acid biosynthesis was measured after insulin was added to the incubation medium of adrenocortical cells isolated from diabetic animals. The results of the present study provide new information about the implication of this abnormal metabolism in the adrenal gland of diabetic rats.
Mol Cell Endocrinol 1991 May
PMID:Abnormal metabolism of polyunsaturated fatty acids in adrenal glands of diabetic rats. 184 41

Cadmium exposure is capable of causing acute and chronic lung injuries, but the specific pathogenetic mechanisms are uncertain. The effects of cadmium ion (Cd2+) on phospholipid metabolism were examined in cultured bovine pulmonary artery endothelial cells (BPAEC), as endothelial cells appear to be particularly vulnerable to the toxic effects of this metallic ion. Exposure of radiolabeled BPAEC to millimolar concentrations of Cd2+ causes liberation of substantial amounts of [3H]arachidonic acid ([3H]AA), but only small amounts of [14C]stearic acid, from each of the major phospholipid subclasses. Analyses of hydrolytic products in BPAEC radiolabeled with [3H]myo-inositol and exposed to Cd2+ indicate that degradation of complex phospholipids is mediated by phospholipase A2. The ability of BPAEC to incorporate fatty acids or lysophosphatides into complex phospholipids is similarly impaired after exposure to Cd2+, suggesting that the liberation of [3H]AA might be due to impairment of reacylation mechanisms and not to increased hydrolytic activity of phospholipase A2. Of the two enzymes involved in reacylation reactions, Cd2+ is found to inhibit the activity of arachidonyl-specific acyl coenzyme A synthetase but not the activity of acyltransferase. Cd2+ also causes a profound time- and dose-dependent depletion of adenosine triphosphate levels in BPAEC, and these changes closely correlate with the liberation of [3H]AA. We suggest that impairment of reacylation mechanisms, and the consequent accumulation of arachidonic acid, may be important in the development of the acute inflammatory reaction that is characteristic of Cd(2+)-induced lung injury.
Am J Respir Cell Mol Biol 1991 Oct
PMID:Cadmium ion-induced alterations of phospholipid metabolism in endothelial cells. 191 Aug 17

Several studies have shown that in animals fed fish oils, docosahexaenoic acid (DHA) is incorporated into cardiac phosphatidylcholines (PC) mainly at the expense of arachidonic acid. In this study we were interested in examining if the enzymatic system involved in the remodeling of membrane PC presented any selectivity for DHA in rat heart. The enzymes that were studied from sequential incubations carried out in parallel, were acyl-CoA synthetase (EC 6.2.1.3) and acyl-CoA:lysophosphatidylcholine acyltransferase (EC 2.3.1.23) (ACLAT). The heart preparations examined were homogenates of whole heart and of purified cultured rat ventricular myocytes. Results showed that ACLAT tended to preferentially incorporate into PC the polyunsaturated fatty acids of the n-6 series (+30%) rather than those of the n-3 series. DHA, however, inhibited the incorporation of arachidonic acid (AA) into PC by 50% at a molar ratio (DHA/AA) of 1.5. This phenomenon seems to be related to the competitive inhibition exerted by DHA on the thio-esterification of AA, a reaction catalyzed by acyl-CoA synthetase. This inhibitory effect appears to be dependent on the kinetic properties of the acyl-CoA synthetase toward DHA which, among the fatty acids examined, exhibited the lowest apparent Km and Vmax. It is suggested that the intracellular pool of DHA-CoA is the determinant species in altering the DHA composition of cardiac PC in animals given fish oils.
Mol Cell Biochem 1990 Mar 27
PMID:In vitro study of docosahexaenoic acid incorporation into phosphatidylcholine by enzymes of rat heart. 197 6

The mechanism of transfer of long chain fatty acids across the myocardial sarcolemmal membrane was investigated in isolated, calcium-resistant, rat cardiomyocytes. The initial rate of 14C-palmitate uptake was determined at constant and increasing palmitate/albumin ratios. The latter condition led to a saturable dependence of uptake rate on palmitate concentration. At a constant palmitate/albumin ratio however, there was an almost constant rate of uptake even though the absolute concentration of palmitate increased. The enhanced metabolic rate resulting from electrically induced contractions of the myocytes decreased the apparent Km of uptake from 62 to 23 microM. Thirty seconds after administration, there was no further increase in the [14C]palmitate content of the myocytes. Moreover, from experiments using ghost membrane vesicles the concentration of palmitate in membranes increased almost linearly with increasing palmitate/albumin ratios. This concentration remained virtually constant if vesicles were pre-treated with diamide. Our results do not support the concept of an albumin receptor-mediated uptake but rather suggest that fatty acids are incorporated into cardiomyocytes by a simple diffusion process which is not rate-limiting. The rate of uptake is influenced both by the metabolic rate and by the concentration of fatty acids in the membranes. The rate-limiting step of fatty acid uptake is probably either the formation of acyl-CoA catalyzed by the membrane associated acyl-CoA synthetase, or the transfer of fatty acid carnitine esters across the mitochondrial matrix membrane.
J Mol Cell Cardiol 1990 Aug
PMID:Sarcolemmal fatty acid transfer in isolated cardiomyocytes governed by albumin/membrane-lipid partition. 217 57

Acyl-CoA synthetase activity with various long-chain fatty acid substrates and its kinetic properties were measured in rat adrenal microsomes. The apparent Michaelis constants (Km) for substrate fatty acids increased in the order eicosa-8,11,14-trienoic acid less than alpha-linolenic acid less than linoleic acid less than palmitic acid. The maximum velocities with these fatty acids decreased in the order linolenic greater than eicosa-8,11,14-trienoic acid greater than palmitic acid. The synthesis of radioactivity palmitoyl-CoA, linoleyl-CoA, alpha-linolenyl-CoA and eicosa-8,11,14-trienoyl-CoA from the respective radioactive substrates decreased in the presence of all the other fatty acids mentioned above. These effects were inversely correlated with their apparent Km values. These results support the idea of a single long-chain fatty acyl-CoA synthetase in the adrenal microsomal fraction for the acid tested. After testing the influence of different hormones, it was shown that the administration of epinephrine, ACTH and dexamethasone caused a significant decrease in the activity of the long-chain fatty acid-CoA synthetase. This inhibition is independent of the one produced by the same hormones on the desaturation of linoleic to gamma-linolenic acid.
Mol Cell Endocrinol 1988 Mar
PMID:Long-chain fatty acyl-CoA synthetase of rat adrenal microsomes. Effect of ACTH and epinephrine. 283 41

The intraerythrocytic malaria parasite depends on the surrounding medium for a supply of phospholipid precursors. Efficient inhibition (IC50 7-90 microM) of Plasmodium falciparum growth in vitro was achieved using modified fatty acids. The fatty acid analogues most effective in suppressing P. falciparum growth in culture were also the most active inhibitors of acyl-CoA synthetase from the monkey parasite P. knowlesi.
Mol Biochem Parasitol 1988 Feb
PMID:Correlation of the efficiency of fatty acid derivatives in suppressing Plasmodium falciparum growth in culture with their inhibitory effect on acyl-CoA synthetase activity. 328 57

Activity of one of the key enzymes involved in arachidonic acid (20:4 n-6) biosynthesis, the delta 5 desaturase, was found in rat liver cell nuclei. Up to now, it has been shown that the fatty acid desaturases are located exclusively in the endoplasmic reticulum. Similarly to what happens with microsomal enzyme the nuclear delta 5 desaturase enzyme was only fully active in the presence of a cytosolic factor. In this condition it reached a specific activity of 50 pmol 20:4 n-6 formed/min/mg of protein. This fact would imply that purified nuclei like purified microsomes lack a soluble cytosol factor necessary for the total desaturation reaction expression. Besides the nuclear delta 5 desaturase has an optimal pH of 7.6 and is inhibited by 1 or 10 mM KCN. Low long chain acyl-CoA synthetase activity that catalyzes the formation of 20:3 n-6-CoA, was also found in liver nuclei. This step would be essential in nuclear desaturation since when ATP and/or CoA (necessary for the acylation reaction) are omitted from the incubation mixture, the desaturation reaction does not take place.
Mol Cell Biochem 1995 Jan 26
PMID:Fatty acid delta 5 desaturation in rat liver cell nuclei. 777 68

Acyl-CoA-binding protein has been isolated independently by five different groups based on its ability to (1) displace diazepam from the GABAA receptor, (2) affect cell growth, (3) induce medium-chain acyl-CoA-ester synthesis, (4) stimulate steroid hormone synthesis, and (5) affect glucose-induced insulin secretion. In this survey evidence is presented to show that ACBP is able to act as an intracellular acyl-CoA transporter and acyl-CoA pool former. The rat ACBP genomic gene consists of 4 exons and is actively expressed in all tissues tested with highest concentration being found in liver. ACBP consists of 86 amino acid residues and contains 4 alpha-helices which are folded into a boomerang type of structure with alpha-helices 1, 2 and 4 in the one arm and alpha-helix 3 and an open loop in the other arm of the boomerang. ACBP is able to stimulate mitochondrial acyl-CoA synthetase by removing acyl-CoA esters from the enzyme. ACBP is also able to desorb acyl-CoA esters from immobilized membranes and transport and deliver these for mitochondrial beta-oxidation. ACBP efficiently protects acetyl-CoA carboxylase and the mitochondrial ADP/ATP translocase against acyl-CoA inhibition. Finally, ACBP is shown to be able to act as an intracellular acyl-CoA pool former by overexpression in yeast. The possible role of ACBP in lipid metabolism is discussed.
Mol Cell Biochem
PMID:The function of acyl-CoA-binding protein (ACBP)/diazepam binding inhibitor (DBI). 823 54


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