Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Weanling rats were fed a riboflavin-deficient diet. The mitochondrial fatty acid oxidation in liver was depressed in riboflavin deficiency but restored after supplementation of riboflavin. Among the enzymes involved in this system, only the acyl-CoA dehydrogenase (EC 1.3.99.2 and 1.3.99.3) activities varied with the change in fatty acid oxidation. An accumulation of the apoforms of acyl-CoA dehydrogenases was found in riboflavin deficiency. The levels of electron transfer flavoprotein and other enzymes involved in the beta-oxidation system remained unchanged. The peroxisomal fatty acid oxidation and levels of individual enzymes of this system remained constant. No accumulation of the apoform of acyl-CoA oxidase was observed under simple, riboflavin-deficient conditions. However, accumulation of a large amount of apo-acyl-CoA oxidase was observed when the peroxisomal system was induced by administration of a peroxisome proliferator, di(2-ethylhexyl)phthalate, under riboflavin-deficient conditions.
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PMID:Riboflavin deficiency and beta-oxidation systems in rat liver. 714 48

A highly sensitive and reliable method for assaying acyl-CoA oxidase (EC 1.3.99.3) activity was developed. An acyl-CoA oxidase-dependent [1-14C]palmitoyl-CoA degradation to acetyl-CoA, acid-soluble products, was measured by coupling with the multienzyme complex for fatty acid oxidation from Pseudomonas fragi. The activity, more than 2 pmol/min, could be assessed using this method. The activity was dependent on the coupling enzyme (multienzyme complex), coenzymes such as NAD+ and CoA, and oxygen, and the interference of acyl-CoA dehydrogenases was excluded. The activity in human samples of cultured skin fibroblasts and lymphocytes was compatible with the expected activity calculated from the amount of acyl-CoA oxidase protein estimated by immunoblot analysis. The method which was verified in several experiments can be used for clinical diagnosis of acyl-CoA oxidase deficiency and for determination of activity in samples with a low level of acyl-CoA oxidase.
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PMID:A sensitive assay of acyl-coenzyme A oxidase by coupling with beta-oxidation multienzyme complex. 781 Aug 78

Studies of effects of 4-thia-substituted fatty acid analogues on rat liver lipid metabolism are described. With isolated hepatocytes tetradecylthiopropionate was shown to divert [1-14C]oleate from beta-oxidation into esterification, the total amount of [1-14C]oleate metabolized remaining unchanged. Tetradecylthiopropionyl-CoA was a good substrate for mitochondrial carnitine palmitoyltransferases I and II (EC 2.3.1.21), acyl-CoA oxidase (EC 1.3.3.6), for the microsomal (but not mitochondrial) glycerophosphate acyltransferase (EC 2.3.1.15), and for long-chain acyl-CoA dehydrogenase (EC 1.3.99.3). In isolated hepatocytes, its 4-thia-trans-2-enoic derivative, tetradecylthioacrylate, inhibits both beta-oxidation of, and incorporation of, [1-14C]oleate into lipids. In rat liver mitochondria tetradecylthiocrylate inhibited beta-oxidation. The degree of inhibition was not markedly increased by preincubation with tetradecylthioacrylate. Tetradecylthioacrylyl-CoA was a poor substrate for carnitine palmitoyltransferase I, and inhibited carnitine palmitoyltransferase II, microsomal glycerophosphate acyltransferase and acyl-CoA oxidase. It is concluded that the inhibitory effects of tetradecylthiopropionyl-CoA are expressed intramitochondrially, whereas primary sites of inhibition by tetradecylthioacrylyl-CoA are extramitochondrial.
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PMID:Effects of tetradecylthiopropionic acid and tetradecylthioacrylic acid on rat liver lipid metabolism. 783 78

Morris 7800 C1 hepatoma cells were grown in the presence of 80 microM tetradecylthioacetic acid (TTA), a peroxisome proliferator, for 1 year (long-term-treated cells). The growth of the Morris 7800 C1 hepatoma cells was inhibited in cells treated with TTA for up to 8 days. Treatment of the cells with TTA for 1 year did not reduce growth further. The growth inhibition was easily reversed by insulin (0.4 microM). Peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity was increased 5.5 times in cells treated with TTA for 3 days. In the cells treated with TTA for 1 year the ACO activity was increased only two times. A similar ACO mRNA half-life (two times the control) was found in cells treated with TTA for 1 year and for 3 days. This implies a loss of effect of TTA on the transcription rate of the ACO gene in long-term-treated cells.
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PMID:The effects of long-term administration of 3-thia fatty acid, a peroxisome proliferator, to Morris 7800 C1 hepatoma cells. 821 84

Synthesis of 32P-labeled CoA of high specific activity was achieved using partially purified dephospho-CoA kinase (EC 2.7.1.24) from pig liver with [gamma-32P]ATP as donor and dephospho-CoA as acceptor. A photoaffinity dodecanoic acid analog, 12-[(4-azidosalicyl)amino]dodecanoic acid was synthesized, as were its CoA derivative (ASD-CoA) and the CoA derivative of 12-azidooleic acid. The CoA derivatives were synthesized from azido fatty acid analogs by acyl-CoA synthetase. The synthesized photolabile reagents were tested as photoaffinity labels for acyl-CoA oxidase (EC 1.3.99.3) from Arthrobacter species. When a mixture of oxidase and the acyl-CoA analogs were incubated in the absence of ultraviolet light, the analogs were recognized as substrate. Acyl-CoA oxidase was incubated in the presence of acyl-CoA analogs and immediately photolyzed, which resulted in irreversible inhibition. Oleoyl-CoA and dodecanoyl-CoA protect the enzyme from photoactivated inhibition by 12-azidooleoyl-CoA and ASD-CoA, respectively. Analysis of photolyzed enzyme preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that both analogs preferentially labeled a 54,000 molecular weight protein. These results demonstrate that the photoaffinity acyl-CoA analogs have potential application as probes to identify and characterize lipid biosynthetic enzymes and to identify the active site of these proteins.
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PMID:Photoaffinity labeling of acyl-CoA oxidase with 12-azidooleoyl-CoA and 12-[(4-azidosalicyl)amino]dodecanoyl-CoA. 824 Nov 27

The 3-thia fatty acid tetradecylthioacetic acid (TTA) has recently been shown to inhibit growth rate and increase peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity in the Morris 7800 C1 hepatoma cells. Dexamethasone potentiates and insulin antagonizes these effects of TTA. We demonstrate here the metabolism of the 3-thia acids in these cells and the influence of insulin and dexamethasone on this. (1) The Morris 7800 C1 hepatoma cells exhibited a low omega-hydroxylation activity of the 3-thia acid (and lauric acid). The combination of TTA and dexamethasone induced the omega-hydroxylation and ACO activities in these cells. TTA alone induced ACO activity, but not omega-hydroxylation activity. Insulin counteracted the induction of both enzyme activities. These results indicate that these two enzyme activities are under similar but independent regulation. (2) Hepatoma cells grown with 80 microM TTA in the medium accumulated phospholipids containing the 3-thia fatty acid. After 7 days, TTA accounted for approx. 40% of the total fatty acids in the phospholipids. In addition, TTA affected the incorporation of endogenous fatty acids into phospholipids by decreasing the amounts of palmitic (C16:0) and vaccenic (C18:1(n-7)) acid and increasing the amounts of linoleic (C18:2(n-6)) and alpha-linolenic (C18:3(n-3)) acid in the phospholipids. (3) Dexamethasone increased the incorporation of labelled TTA into both phospholipids and triacylglycerol. Most of the labelled triacylglycerol formed was secreted into the medium. Insulin increased the incorporation of labelled TTA into triacylglycerol, but not into phospholipids. The labelled triacylglycerol formed was retained in the cells.
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PMID:Hormonal and substrate regulation of 3-thia fatty acid metabolism in Morris 7800 C1 hepatoma cells. 837 45

The activity of the enzyme acyl-CoA oxidase (EC 1.3.99.3) is influenced by detergents. At concentrations above the critical micellar concentration, Triton X-100, Triton X-114 and Thesit stimulate oxidase activity. Lower concentrations of Triton X-100 and Triton X-114 render the acyl-CoA oxidase less sensitive towards substrate inhibition by palmitoyl-CoA or dec-4-cis-enoyl-CoA. Other detergents inhibited the enzyme activity. CoA was found to be a relatively powerful competitive inhibitor of the enzyme, with a Ki,slope value of 63 +/- 3 microM. This inhibition is dependent on an intact CoA molecule, as dephospho-CoA, dethio-CoA and acetyl-CoA are less potent inhibitors of the enzyme. Dec-2-trans-enoyl-CoA is a product-inhibitor of acyl-CoA oxidase, with a Ki,slope value of 7 +/- 1 microM.
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PMID:Factors which affect the activity of purified rat liver acyl-CoA oxidase. 843 1

The activities of hepatic fatty acid oxidation enzymes in rats fed perilla oil rich in alpha-linolenic acid (alpha-18:3) were compared with those fed saturated fats or safflower oil (the mixture of safflower oil and olive oil, 94:8, w/w) containing the same amount of polyunsaturated fatty acids with perilla oil exclusively as linoleic acid (18:2). When the rats were fed the diets containing 15% coconut, safflower, and perilla oils for 1 week, the rate of mitochondrial and peroxisomal oxidation of palmitoyl-CoA (16:0-CoA) in the liver homogenates was the highest in rats fed perilla oil. Among the rats fed the diets containing 15% palm, safflower, and perilla oils for 2 weeks, the rates of mitochondrial and peroxisomal oxidations of 16:0-, 18:2-, and alpha-18:3-CoAs were the highest in rats fed perilla oil, and the rate of oxidation of alpha-18:3-CoA by both pathways was higher than those of other acyl-CoAs in all groups. Dietary perilla oil relative to palm and safflower oils significantly increased the activities of carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, and 2,4-dienoyl-CoA reductase. The substrate specificity of carnitine palmitoyltransferase appeared to be responsible for differential rates of the mitochondrial oxidation of acyl-CoAs. The substrate specificity of acyl-CoA oxidase did not account for the preferential peroxisomal oxidation of alpha-18:3 relative to 18:2. The preferential mitochondrial and peroxisomal beta-oxidation of alpha-18:3-CoA relative to 16:0- and 18:2-CoAs was also confirmed in rats fed laboratory chow irrespective of the substrate/albumin ratios in the assay mixture. It was suggested that both substrate specificities and alterations in the activities of the enzymes in beta-oxidation pathway play a significant role in the regulation of the serum lipid concentrations in rats fed a diet rich in alpha-18:3.
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PMID:Stimulation of the activities of hepatic fatty acid oxidation enzymes by dietary fat rich in alpha-linolenic acid in rats. 872 10

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is one of four straight-chain acyl-CoA dehydrogenase (ACD) enzymes, which are all nuclear encoded mitochondrial flavoproteins catalyzing the initial step in fatty acid beta-oxidation. We have used the very fast, Rapid Amplification of cDNA Ends (RACE) based strategy to obtain the sequence of cDNAs encoding human VLCAD from placenta and fibroblasts. Alignment of the predicted amino acid sequence of human VLCAD with those of the other human ACD enzymes revealed extensive sequence homology. Moreover, human VLCAD and human acyl-CoA oxidase showed extensive sequence homology corroborating the notion that these genes are evolutionarily related. Southern blot analysis of genomic DNA from hybrid cell lines was used to localize the VLCAD gene to human chromosome 17p11.2-p11.13105. Using Northern and Western blot analysis to investigate the tissue specific distribution of VLCAD mRNA and protein in several human tissues we showed that VLCAD is most abundant in heart and skeletal muscle. This agrees well with the fact that cardiac and muscle symptoms are characteristic for patients with VLCAD deficiency. Northern blot analysis and sequencing of cloned PCR amplified VLCAD cDNA from four unrelated patients with VLCAD deficiency showed that VLCAD mRNA was undetectable in one patient and that the other three have mutations in both VLCAD alleles. Western blot analysis of patient fibroblasts showed that the identified mutations result in severely reduced amounts of VLCAD protein. None of the patients harbored identical mutations suggesting that the mutational heterogeneity in VLCAD deficiency is large.
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PMID:Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene. 884 38

The activities of enzymes in fatty acid oxidation and synthesis in the liver of rats fed soybean phospholipids and soybean oil corresponding to the dietary levels of 3% fatty acid added to the diets containing a saturated fat (coconut oil) and a polyunsaturated fat (safflower oil) at the amounts corresponding to 12% fatty acid levels were compared. Soybean phospholipid compared with soybean oil added to both coconut and safflower oil diets significantly reduced the activities of enzymes in fatty acid synthesis (fatty and synthetase, glucose-6-phosphate dehydrogenase and malic enzyme). However, there were no significant differences in the activities of enzymes in fatty acid oxidation (carnitine palmitoyltransferase, acyl-CoA dehydrogenase and acyl-CoA oxidase) between the groups of rats fed soybean phospholipid and soybean oil added to coconut and safflower oil diets except for one occasion. Soybean phospholipid compared with soybean oil added to coconut oil diet significantly decreased the concentrations of triacylglycerol, cholesterol and phospholipid in the serum and of triacylglycerol and cholesterol in the liver. However, the dietary phospholipid added to safflower oil diet failed to alter these values. These results suggested that the alteration in the rate of fatty acid synthesis, but not oxidation, in the liver is responsible for the lipid-lowering effect of dietary soybean phospholipid added to a saturated fat diet.
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PMID:Effect of dietary soybean phospholipid and fats differing in the degree of unsaturation on fatty acid synthesis and oxidation in rat liver. 892 36


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