Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The activities of peroxisomal and mitochondrial beta-oxidation and carnitine acyltransferases changed during the process of development from embryo to adult chicken, and the highest activities of peroxisomal beta-oxidation, palmitoyl-CoA oxidase, and carnitine acetyltransferase were found at the hatching stage of the embryo. The profiles of these alterations were in agreement with those of the contents of triglycerides and free fatty acids in the liver. The highest activities of mitochondrial beta-oxidation and palmitoyl-CoA dehydrogenase were observed at the earlier stages of the embryo; then the activities decreased gradually from embryo to adult chicken. The ratio of activities of carnitine acetyltransferase in peroxisomes and mitochondria (peroxisomes/mitochondria) increased from 0.54 to 0.82 during the development from embryo to adult chicken. The ratio of activities of carnitine palmitoyltransferase decreased from 0.82 to 0.25 during the development. The affinity of fatty acyl-CoA dehydrogenase toward the medium-chain acyl-CoAs (C6 and C8) was high in the embryo and decreased with development, whereas the substrate specificity of fatty acyl-CoA oxidase did not change. The substrate specificity of mitochondrial carnitine acyltransferases did not change with development. The affinity of peroxisomal carnitine acyltransferases toward the long-chain acyl-CoAs (C10 to C16) was high in the embryo, but low in adult chicken.
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PMID:Developmental changes in the activities of peroxisomal and mitochondrial beta-oxidation in chicken liver. 397 May 42

The activities of antimycin A-insensitive palmitoyl-CoA oxidation and of palmitoyl-CoA oxidase in peroxisomes from chicken liver were similar to those of rat liver. Catalase and D-amino acid oxidase activities in peroxisomes from chicken liver were lower than those of rat liver, and urate oxidase was not detected. Carnitine acetyl-transferase and palmitoyltransferase levels in chicken liver were 18- and 2-fold higher, respectively, than those of rat liver. Peroxisomal palmitoyl-CoA oxidation of chicken liver was inhibited by cyanide, in contrast to that of rat liver, although it was insensitive to antimycin A. Subcellular distribution of this enzyme was similar to that of rat liver; i.e., it was located only in the peroxisomes. The fatty acyl-CoA oxidase had a higher affinity toward medium- to long-chain fatty acyl-CoAs (C8 to C16) than shorter-chain analogs. The fatty acyl-CoA dehydrogenase had a broad affinity toward fatty acyl-CoAs (C4 to C18). Carnitine acetyltransferase was distributed equally in both peroxisomes and mitochondria. Carnitine palmitoyltransferase was distributed in the proportion of 20 and 80% in peroxisomes and mitochondria, respectively.
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PMID:Peroxisomal fatty acyl-coenzyme A oxidation in chicken liver. 613 87

Rats treated with six to eight doses (80 mg/kg, i.p.) of 4-pentenoic acid, an inhibitor of mitochondrial fatty acid oxidation in vitro, during a 48-hr starvation period developed microvesicular fatty infiltration of the liver similar to that observed in Reye's Syndrome. Hepatic triglycerides were elevated an average of 5-fold, although considerable variability was found between individual rats. Fed rats did not develop fatty liver upon similar treatment with pentenoic acid. Liver mitochondria isolated from rats with pentenoic acid-induced fatty liver showed a persistent inhibition of fatty acid oxidation. Rates of oxidation of palmitoylcarnitine and decanoylcarnitine were decreased about 70%, while that of octanoylcarnitine was decreased 50%. Carnitine-independent oxidation of octanoate was also inhibited. Oxidation rates for substrates other than fatty acids, including glutamate, succinate, pyruvate, and alpha-ketoglutarate, were unaffected. Measurements of flavoprotein reduction in intact mitochondria indicated that neither palmitoylcarnitine nor palmitoyl CoA plus L-carnitine could elicit reduction of acyl-CoA dehydrogenase and electron transferring flavoprotein in mitochondria from rats with pentenoic acid-induced fatty liver. These results support a site of inhibition of mitochondrial beta-oxidation at the level of acyl-CoA dehydrogenase for pentenoic acid treatment in vivo, and they suggest a role for nutritional or hormonal factors in the metabolic disposition of pentenoic acid in vivo and in the development of fatty liver.
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PMID:Inhibition of mitochondrial fatty acid oxidation in pentenoic acid-induced fatty liver. A possible model for Reye's syndrome. 671 30

Linoleate monohydroperoxide (L-HPO), methyl linoleate monohydroperoxide (ML-HPO), and methyl hydroperoxy-epoxy-octadecenoate (ML-X) inhibited state 3 respiration of mitochondria when palmitate, palmitoyl CoA, or L-palmitoylcarnitine was used as a substrate. L-HPO was the most effective, and 50% inhibition of palmitate-supported respiration was observed with 2, 3.3, and 6.5 nmol/mg protein of L-HPO, ML-X, and ML-HPO, respectively. Almost the same values were obtained when palmitoyl CoA or L-palmitoylcarnitine was used in place of palmitate. L-HPO inhibited the reaction of beta-oxidation in mitochondria in a similar concentration range (4 nmol/mg protein for 50% inhibition) when L-palmitoylcarnitine was used as a substrate. L-HPO also inhibited the formation of 3-hydroxypalmitoylcarnitine from the same substrate. Carnitine palmitoyltransferase activity of mitochondria was inhibited by L-HPO, 50% inhibition occurring at 12 nmol/mg protein. These inhibitory effects of L-HPO were weaker when ATP was removed by hexokinase and glucose. ATP-dependent formation of carnitine ester of L-HPO was also suggested. It was deduced that L-HPO (and ML-X and ML-HPO after hydrolysis) was converted to carnitine ester and inhibited the palmitate metabolism at the site(s) of intramitochondrial carnitine palmitoyltransferase (and possibly acyl CoA dehydrogenase).
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PMID:Inhibition of palmitate oxidation in mitochondria by lipid hydroperoxides. 672 34

2-Methyl-branched chain acyl-CoA dehydrogenase was purified to homogeneity from rat liver mitochondria. The native molecular weight of the enzyme was estimated to be 170,000 by gel filtration. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis both with and without 2-mercaptoethanol, the enzyme showed a single protein band with Mr = 41,500, suggesting that this enzyme is composed of four subunits of equal size. Its isoelectric point was 5.50 +/- 0.2, and A1%280 nm was 12.5. This enzyme contained protein-bound FAD. The purified enzyme dehydrogenated S-2-methylbutyryl-CoA and isobutyryl-CoA with equal activity. The activities with each of these compounds were co-purified throughout the entire purification procedure. This enzyme also dehydrogenated R-2-methylbutyryl-CoA, but the specific activity was considerably lower (22%) than that for the S-enantiomer. The enzyme did not dehydrogenate other acyl-CoAs, including isovaleryl-CoA, propionyl-CoA, butyryl-CoA, octanoyl-CoA, and palmitoyl-CoA, at any significant rate. Apparent Km and Vmax values for S-2-methylbutyryl-CoA were 20 microM and 2.2 mumol min-1 mg-1, respectively, while those for isobutyryl-CoA were 89 microM and 2.0 mumol min-1 mg-1 using phenazine methosulfate as an artificial electron acceptor. The enzyme was also active with electron transfer flavoprotein. Tiglyl-CoA and methacrylyl-CoA were identified as the reaction products from S-2-methylbutyryl-CoA and isobutyryl-CoA, respectively. 2-Ethylacrylyl-CoA was produced from R-2-methylbutyryl-CoA. Tiglyl-CoA competitively inhibited the activity with both S-2-methylbutyryl-CoA and isobutyryl-CoA with a similar Ki. The enzyme activity was also severely inhibited by several organic sulfhydryl reagents such as N-ethylmaleimide, p-hydroxymercuribenzoate, and methyl mercury iodide. The pattern and degree of inhibition were essentially identical for both substrates. The purified 2-methyl-branched chain acyl-CoA dehydrogenase was immunologically distinct from isovaleryl-CoA-, short chain acyl-CoA-, medium chain acyl-CoA-, or long chain acyl-CoA dehydrogenase.
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PMID:Purification and characterization of 2-methyl-branched chain acyl coenzyme A dehydrogenase, an enzyme involved in the isoleucine and valine metabolism, from rat liver mitochondria. 687 97

The interaction of two long-chain acyl-CoA analogs with pig kidney general acyl-CoA dehydrogenase (EC 1.3.99,3) was examined. The effect of S-heptadecyl-CoA and heptadecan-2-onyl-dethio-CoA on the flavo-protein was observed spectrophotometrically using the flavin as an active-site probe. The S-heptadecyl thioether analog bound strongly to the enzyme (Kd = 17 nM) and was a powerful competitive inhibitor (Ki less than 40 nM). In contrast to the thioether analog, the dethiocarba derivative, heptadecan-2-onyl-dethio-CoA, was a substrate inthe standard assay system being dehydrogenated at about 60% of the rate shown by palmitoyl-CoA. These results support the proposal that alpha-carbanion formation is an early event in the dehydrogenation of acyl-CoA substrates.
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PMID:Interaction of long-chain acyl-CoA analogs with pig kidney general acyl-CoA dehydrogenase. 728 23

Pig kidney general acyl-CoA dehydrogenases forms the blue neutral radical on dithionite or photochemical reduction (Thorpe, C., Matthews, R. G., & Williams, C. H. (1979) Biochemistry 18, 331-337] in accord with its classification as a flavoprotein dehydrogenase. However, dithionite reduction of the enzyme in the presence of crotonyl coenzyme A (crotonyl-CoA) or octenoyl-CoA generates the red radical anion as the predominant species at pH 7.6. Crotonyl-CoA binds preferentially to the red radical form, depressing the apparent pK by at least 2.5 pH units to a value of 7.3. Butyryl-, octanoyl-, and palmitoyl-CoA induce very similar spectral changes to those induced by enoyl-CoA derivatives when added anaerobically to the blue semiquinone enzyme. In contrast, the competitive inhibitors acetoacetyl-CoA and heptadecyl-SCoA do not markedly perturb the spectrum of the neutral flavosemiquinone species. The stability of the enzyme radical complexes with either crotonyl- or octanoyl-CoA suggests that there is not effective intraflavin transfer of reducing equivalents between subunits. Perturbation of the spectrum of the one-electron-reduced enzyme by ligands may complicate interpretation of the reaction enzyme by ligands may complicate interpretation of the reaction between substrate complexes of the general acyl-CoA dehydrogenase and electron-transferring flavoprotein.
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PMID:Stabilization of the red semiquinone form of pig kidney general acyl-CoA dehydrogenase by acyl coenzyme A derivatives. 729 60

Negative chemical ionization (NCI) mass spectrometry was used to quantify the acyl-CoA intermediates present in human fibroblasts growing in media containing the long-chain fatty acid, palmitate. The acyl-CoA intermediates were detected as the N-acyl pentafluorobenzyl glycinates. In fibroblasts from normal individuals only saturated acyl-CoA esters were detected, supporting the concept that the acyl-CoA dehydrogenase reaction is the rate-limiting step of intramitochondrial fatty acid oxidation. In patients with inherited enzymatic defects of intramitochondrial long-chain fatty acid oxidation, there was not a significant increase in the amount of long-chain acyl-CoA compounds, with palmitoyl-CoA amounts similar to those found in controls. However, there was a sharp decrease in the relative amount of lauroyl-CoA and a resultant sixfold elevation in the palmitoyl-CoA:lauroyl-CoA ratio. In contrast, fibroblasts with a defect involving the transport of fatty acids across the mitochondrial membrane, carnitine palmitoyl transferase 1 deficiency, had a fourfold increase in palmitoyl-CoA. Our results suggest that acyl-CoA esters in biological tissues are readily detectable using NCI mass spectrometry. This approach is significantly more sensitive than previous methods for the detection of these important metabolic intermediates, and may prove useful in the study of fatty acid oxidation in both normal and enzyme-deficient tissues.
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PMID:Long-chain acyl-CoA profiles in cultured fibroblasts from patients with defects in fatty acid oxidation. 755 21

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

Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of fatty acid beta-oxidation. Its diagnosis has been made based on the reduced activity of palmitoyl-CoA dehydrogenation, i.e., in fibroblasts. We previously showed that in immunoblot analysis, an LCAD band of normal size and intensity was detected in fibroblasts from all LCAD-deficient patients tested. In the present study, we amplified via polymerase chain reaction and sequenced LCAD cDNA from three of these LCAD-deficient cell lines, and found perfectly normal LCAD sequences in two of them, indicating that at least these patients were not deficient in LCAD. The third patient was homozygous for an A to C substitution at 997, although it is unknown whether or not 997-C is a normal polymorphism. Although the LCAD sequence data were puzzling, a new enzyme, very-long-chain acyl-CoA dehydrogenase (VLCAD), was recently identified. Because VLCAD also has high activity with palmitoyl-CoA as substrate, it was possible that defective VLCAD may cause reduced palmitoyl-CoA dehydrogenating activity. We performed immunoblot analysis of VLCAD in six "LCAD-deficient" patients; VLCAD was negative in three of them, two of whom had a normal LCAD cDNA sequence. These results indicated that a considerable number of the patients who had previously been diagnosed as having LCAD deficiency in fact have VLCAD deficiency.
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PMID:Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency. 835 11


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