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

In control rats, long-chain monocarboxylyl-CoA, omega-hydroxymonocarboxylyl-CoA, and dicarboxylyl-CoA esters were substrates for hepatic, renal, and myocardial peroxisomal beta-oxidation. The latter enzyme system could not be detected in skeletal muscle. Clofibrate treatment resulted in an enhancement of peroxisomal beta-oxidizing capacity in various tissues. Intact mitochondria from control rat liver and kidney cortex incubated in the presence of L-carnitine were capable of oxidizing long-chain monocarboxylyl-CoAs and omega-hydroxymonocarboxylyl-CoAs but not dicarboxylyl-CoAs. However, control rat liver mitochondria permeabilized by digitonin oxidized dodecanedioyl-CoA indicating that the liver mitochondrial beta-oxidation system can act on dicarboxylyl-CoA esters even if the overall intact mitochondrial system is inactive on these substrates. Intact liver mitochondria from clofibrate-treated animals rapidly oxidized lauroyl-CoA and 12-hydroxylauroyl-CoA but not dodecanedioyl-CoA. These mitochondria were active on hexadecanedioyl-CoA and this activity amounted to 20-25% of that measured with palmitoyl-CoA and 16-hydroxypalmitoyl-CoA as substrates. No mitochondrial dicarboxylyl-CoA oxidation could be detected in kidney cortex from animals receiving clofibrate in their diet. Heart and skeletal muscle intact mitochondria from untreated and clofibrate-treated rats were capable of oxidizing each type of acyl-CoA as a substrate. Dicarboxylyl-CoA synthetase and carnitine dicarboxylyltransferase activities were detected in various tissues from untreated and clofibrate-treated rats with the exception of carnitine dodecanedioyltransferase reaction in livers from untreated and clofibrate-treated rats. In skeletal muscle, the acyl-CoA synthetase activities could be detected only in the presence of detergents.
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PMID:Peroxisomal and mitochondrial beta-oxidation of monocarboxylyl-CoA, omega-hydroxymonocarboxylyl-CoA and dicarboxylyl-CoA esters in tissues from untreated and clofibrate-treated rats. 280 18

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.
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PMID:Long-chain fatty acyl-CoA synthetase of rat adrenal microsomes. Effect of ACTH and epinephrine. 283 41

Key enzymes involved in oxidation and esterification of long-chain fatty acids were investigated in male rats fed different types and amounts of oil in their diet. A diet with 20% (w/w) fish oil, partially hydrogenated fish oil (PHFO) and partially hydrogenated soybean oil (PHSO) was shown to stimulate the mitochondrial and microsomal palmitoyl-CoA synthetase activity (EC 6.2.1.3) compared to soybean oil-fed animals after 1 week of feeding. Rapeseed oil had no effect. Partially hydrogenated oils in the diet resulted in significantly higher levels of mitochondrial glycerophosphate acyltransferase compared to unhydrogenated oils in the diet. Rats fed 20% (w/w) rapeseed oil had a decreased activity of this mitochondrial enzyme, whereas the microsomal glycerophosphate acyltransferase activity was stimulated to a comparable extent with 20% (w/w) rapeseed oil, fish oil or PHFO in the diet. Increasing the amount of PHFO (from 5 to 25% (w/w)) in the diet for 3 days led to increased mitochondrial and microsomal palmitoyl-CoA synthetase and microsomal glycerophosphate acyltransferase activities with 5% of this oil in the diet. The mitochondrial glycerophosphate acyltransferase was only marginally affected by increasing the oil dose. Administration of 20% (w/w) PHFO increased rapidly the mitochondrial and microsomal palmitoyl-CoA synthetase, carnitine palmitoyltransferase and microsomal glycerophosphate acyltransferase activities almost to their maximum value within 36 h. In contrast, the glycerophosphate acyltransferase and palmitoyl-CoA hydrolase (EC 3.1.2.2) activities of the mitochondrial fraction and the peroxisomal beta-oxidation reached their maximum activities after administration of the dietary oil for 6.5 days. This sequence of enzyme changes (a) is in accordance with the proposal that an increased cellular level of long-chain acyl-CoA species act as metabolic messages for induction of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase, i.e., these enzymes are regulated by a substrate-induced mechanism, and (b) indicates that, with PHFO, a greater part of the activated fatty acids are directed from triacylglycerol esterification and hydrolysis towards oxidation in the mitochondria. It is also conceivable that the mitochondrial beta-oxidation is proceeding before the enhancement of peroxisomal beta-oxidation.
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PMID:Rapid stimulation of liver palmitoyl-CoA synthetase, carnitine palmitoyltransferase and glycerophosphate acyltransferase compared to peroxisomal beta-oxidation and palmitoyl-CoA hydrolase in rats fed high-fat diets. 289 61

Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.
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PMID:Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver. 297 12

Purified rat brain microvessels were prepared to demonstrate the occurrence of acyl-CoA (EC 6.2.1.3) synthesis activity in the microvasculature of rat brain. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities showed an absolute requirement for ATP and CoA. This activity was strongly enhanced by magnesium chloride and inhibited by EDTA. The apparent Km values for acyl-CoA synthesis by purified rat brain microvessels were 4.0 microM and 5.8 microM for palmitic acid and arachidonic acid, respectively. The apparent Vmax values were 1.0 and 1.5 nmol X min-1 X mg protein-1 for palmitic acid and arachidonic acid, respectively. Cross-competition experiments showed inhibition of radiolabelled arachidonoyl-CoA formation by 15 microM unlabelled arachidonic acid, with a Ki of 7.1 microM, as well as by unlabelled docosahexaenoic acid, with a Ki of 8.0 microM. Unlabelled palmitic acid and arachidic acid had no inhibitory effect on arachidonoyl-CoA synthesis. In comparison, radiolabelled palmitoyl-CoA formation was inhibited competitively by 15 microM unlabelled palmitic acid, with a Ki of 5.0 microM and to a much lesser extent by arachidonic acid (Ki, 23 microM). The Vmax of palmitoyl-CoA formation obtained on incubation in the presence of the latter fatty acids was not changed. Unlabelled arachidic acid and docosahexaenoic acid had no inhibitory effect on palmitoyl-CoA synthesis. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities were thermolabile. Arachidonoyl-CoA formation was inhibited by 75% after 7 min at 40 degrees C whereas a 3-min heating treatment was sufficient to produce the same relative inhibition of palmitoyl-CoA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arachidonoyl-coenzyme A synthetase and nonspecific acyl-coenzyme A synthetase activities in purified rat brain microvessels. 310 92

As part of a long-term study of sphingolipid metabolism in brain, we have purified and partially characterized a long-chain acyl-CoA synthetase from microsomes of developing rat brain and compared it with the hepatic microsomal enzyme from the same animals. Both enzymes were solubilized from microsomes by treatment with Triton X-100 and then chromatographed successively on Blue-Sepharose and DEAE-Sepharose. Blue-Sepharose chromatography yielded a single peak with acyl-CoA synthetase activity, whereas DEAE-Sepharose chromatography of both brain and liver preparations yielded two peaks. Elution patterns of lignoceroyl-CoA synthetase and palmitoyl-CoA synthetase activities were identical throughout these steps and were similar in brain and liver. Gel filtration of each DEAE-Sepharose fraction on Sephadex G-200 also yielded two peaks of activity. The more rapidly eluted material contained much more lignoceroyl-CoA synthetase activity, while the activity for palmitoyl-CoA synthetase was higher in slower eluting peaks. In all preparations the ratio of lignoceroyl-CoA synthetase activity to palmitoyl-CoA synthetase activity was much higher in brain than in liver. These results suggest that although the brain acyl-CoA synthetase is chromatographically similar to the liver enzyme, there are differences in substrate specificity.
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PMID:Lignoceroyl-coenzyme A synthetase from developing rat brain: partial purification, characterization and comparison with palmitoyl-coenzyme A synthetase activity and liver enzyme. 316 45

We previously reported that in childhood adrenoleukodystrophy (C-ALD) and adrenomyeloneuropathy (AMN), the peroxisomal beta-oxidation system for very long chain (greater than C22) fatty acids is defective. To further define the defect in these two forms of X chromosome-linked ALD, we examined the oxidation of [1-14C]lignoceric acid (n-tetracosanoic acid, C24:0) and [1-14C]lignoceroyl-CoA (substrates for the first and second steps of beta-oxidation, respectively). The oxidation rates of lignoceric acid in C-ALD and AMN were 43% and 36% of control values, respectively, whereas the oxidation rate of lignoceroyl-CoA was 109% (C-ALD) and 106% (AMN) of control values, respectively. On the other hand, the oxidation rates of palmitic acid (n-hexadecanoic acid) and palmitoyl-CoA in C-ALD and AMN were similar to the control values. These results suggest that lignoceroyl-CoA ligase activity may be impaired in C-ALD and AMN. To identify the specific enzymatic deficiency and its subcellular localization in C-ALD and AMN, we established a modified procedure for the subcellular fractionation of cultured skin fibroblasts. Determination of acyl-CoA ligase activities provided direct evidence that lignoceroyl-CoA ligase is deficient in peroxisomes while it is normal in mitochondrial and microsomes. Moreover, the normal oxidation of lignoceroyl-CoA as compared with the deficient oxidation of lignoceric acid in isolated peroxisomes also supports the conclusion that peroxisomal lignoceroyl-CoA ligase is impaired in both C-ALD and AMN. Palmitoyl-Coa ligase activity was found to be normal in peroxisomes as well as in mitochondria and microsomes. This normal peroxisomal palmitoyl-CoA ligase activity as compared with the deficient activity of lignoceroyl-CoA ligase in C-ALD and AMN suggests the presence of two separate acyl-CoA ligases for palmitic and lignoceric acids in peroxisomes. These data clearly demonstrate that the pathognomonic accumulation of very long chain fatty acids in C-ALD and AMN is due to a deficiency of peroxisomal very long chain (lignoceric acid) acyl-CoA ligase.
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PMID:Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy. 317 58

The effect of Triton X-100 on the activities and apparent molecular size of fatty acyl-CoA synthetase, solubilized and partially purified from rat liver microsomes, was studied. In the presence of Triton X-100, the activity for lignoceroyl-CoA synthesis was decreased, but activity was restored when the detergent was removed. The appearance and disappearance of lignoceroyl-CoA synthesis appeared related to the size of the aggregated form of the enzyme. On the other hand, activity for palmitoyl-CoA synthesis was not significantly affected by the detergent. Because available evidence suggests that both fatty acids are converted to CoA esters by the same enzyme, it seems likely that the substrate specificity of the enzyme is influenced by changes in the aggregation state and that the microenvironment of the enzyme in membranes may determine the substrate specificity of acyl-CoA synthetase.
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PMID:Change of substrate specificity of rat liver microsomal fatty acyl-CoA synthetase activity by Triton X-100. 372 69

Evidence is presented that the murine thymoma EL4 and cytotoxic T lymphocyte clones possess two distinct long-chain fatty acyl-CoA synthetase activities. One enzyme shows activity toward a broad spectrum of fatty acid substrates, similar to the long-chain fatty acyl-CoA synthetase from rat liver. The other enzyme is selective for arachidonic acid and related fatty acids. Fatty acid competition studies using EL4 microsomes demonstrate that [14C]palmitoyl-CoA synthesis (Km = 13 +/- 1 microM, Vmax = 7 +/- 1 nmol/mg per min) is inhibited by unlabeled palmitate, oleate, linoleate or linolenate (Ki = 15-25 microM) and weakly by arachidonate (Ki greater than 100 microM). Similar inhibition is observed for the activation of [14C]oleate (Km = 31 +/- 3 microM, Vmax = 6 +/- 2 nmol/mg per min). On the other hand, [14C]arachidonyl-CoA synthetase (Km = 15 +/- 3 microM, Vmax = 13 +/- 2 nmol/mg per min) is inhibited by unlabeled arachidonic acid (Ki = 20 microM) but not by unlabeled palmitate, oleate, linoleate and linolenate. The description of arachidonoyl-CoA synthetase in cytotoxic T lymphocyte clones represents the first example of a cell with little or no capacity to synthesize arachidonic acid metabolites, yet which possesses a selective esterification mechanism for the fatty acid. Studies on the specificity of the arachidonic acid-selective acyl-CoA synthetase utilized arachidonic acid metabolites and structurally related fatty acids and yielded two points of interest: (1) metabolism of arachidonic acid to monohydroxy fatty acids (HETEs) resulted in compounds with significantly decreased ability to be activated by the arachidonate-selective acyl-CoA synthetase; (2) arachidonate was a much better substrate than was 5,8,11-eicosatrienoic acid (Km = 41 microM), the fatty acid which accumulates during essential fatty acid deficiency. The possible role of an arachidonic acid-selective acyl-CoA synthetase in lymphocyte activation and as a homeostatic mechanism during essential fatty acid deficiency is discussed.
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PMID:Characterization of an arachidonic acid-selective acyl-CoA synthetase from murine T lymphocytes. 391 71

The fatty acid specificity of acyl-CoA synthetase in rat glomeruli for physiologically and pathologically important long-chain fatty acids was studied. The apparent Michaelis constants (Km) for substrate fatty acids increased in the order, linolenic less than linoleic less than eicosapentaenoic less than arachidonic less than oleic less than palmitic acid. The maximum velocities with these fatty acids decreased in the order, oleic greater than linoleic greater than palmitic (approximately equal to) linolenic greater than arachidonic greater than eicosapentaenoic acid. The syntheses of radioactive arachidonyl-CoA and palmitoyl-CoA from radioactive arachidonic and palmitic acid, respectively, were both inhibited by all fatty acids mentioned above including the substrate fatty acids, their inhibitory effects being inversely correlated with their apparent Km values. These results suggest that the enzyme in glomeruli has a unique specificity for fatty acids and that there is no arachidonic acid-specific acyl-CoA synthetase in glomeruli. The possible contribution of the glomerular enzyme with this specificity to the abnormal fatty acid levels in diabetic animals is discussed.
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PMID:Fatty acid specificity of acyl-CoA synthetase in rat glomeruli. 394 68


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