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)

Aspergillus nidulans is able to grow on oleic acid as sole carbon source. Characterization of the oleate-induced beta-oxidation pathway showed the presence of the two enzyme activities involved in the first step of this catabolic system: acyl-CoA oxidase and acyl-CoA dehydrogenase. After isopicnic centrifugation in a linear sucrose gradient, microbodies (peroxisomes) housing the beta-oxidation enzymes, isocitrate lyase and catalase were clearly resolved from the mitochondrial fraction, which contained fumarase. Growth on oleic acid was associated with the development of many microbodies that were scattered throughout the cytoplasm of the cells. These microbodies (peroxisomes) were round to elongated, made up 6% of the cytoplasmic volume, and were characterized by the presence of catalase. The beta-oxidation pathway was also induced in acetate-grown cells, although at lower levels; these cells lacked acyl-CoA oxidase activity. Nevertheless, growth on acetate did not cause a massive proliferation of microbodies in A. nidulans.
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PMID:Induction of beta-oxidation enzymes and microbody proliferation in Aspergillus nidulans. 892 80

The activity of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in alpha-linolenic acid (alpha-18:3) was compared to that in rats fed safflower oil rich in linoleic acid (18:2) and a saturated fat (palm oil). Palm and safflower oils were essentially devoid of alpha-18:3. The palmitoyl-CoA oxidation rates both in mitochondrial and peroxisomal pathways in liver homogenates were significantly higher in rats fed linseed oil than in those fed palm and safflower oils. Among rats fed diets containing palm oil, safflower oil, fat mixtures composed of safflower and perilla oils (2:1, w/w and 1:2, w/w), and perilla oil, mitochondrial and peroxisomal fatty oxidation rates increased with increasing dietary levels of perilla oil. Compared to palm and safflower oils, dietary alpha-18:3 either in the form of linseed or perilla oils profoundly increased the activity of carnitine palmitoyltransferase, acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, and 2,4-dienoyl-CoA reductase. Smaller but significant increases by dietary alpha-18:3 of the activity of acyl-CoA dehydrogenase, enoyl-CoA hydratase, and delta 3, delta 2-enoyl-CoA isomerase were also observed. Unexpectedly, dietary alpha-18:3 greatly reduced the activity of 3-hydroxy-acyl-CoA dehydrogenase. Compared to palm oil, dietary polyunsaturated fats significantly reduced the activity of fatty acid synthetase and glucose-6-phosphate dehydrogenase to the same levels. The activity of pyruvate kinase was significantly higher in rats fed palm oil than in those fed polyunsaturated fats. The extent of reduction was more prominent with polyunsaturated fats containing alpha-18:3 than with safflower oil devoid of alpha-18:3. Thus, compared to linoleic acid and saturated fatty acids, dietary alpha-18:3 caused characteristic changes in the activity of hepatic enzymes in fatty acid and glucose metabolism in rats.
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PMID:Activity of hepatic fatty acid oxidation enzymes in rats fed alpha-linolenic acid. 895 34

The activities of hepatic enzymes of fatty acid synthesis and oxidation were compared in rats fed on diacylglycerol and triacylglycerol. In the first trial, rats were fed on diacylglycerol or triacylglycerol (rapeseed oil) for 14 d. The diacylglycerol preparation contained 65.2 g and 32.6 g fatty acids/100 g total fatty acids as 1,3-species and 1,2-species respectively. Fatty acid compositions of these dietary lipids were similar. Dietary acylglycerols were added to experimental diets to provide the same amounts of fatty acids (93.9 g/kg diet). Dietary diacylglycerol compared with triacylglycerol significantly reduced the concentrations of serum and liver triacylglycerol. The activities of enzymes of fatty acid synthesis (fatty acid synthetase, glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and malic enzyme (EC 1.1.1.40)) were significantly lower in rats fed on diacylglycerol than in those fed on triacylglycerol. In contrast, the rates of mitochondrial and peroxisomal oxidation of palmitoyl-CoA in liver homogenates were higher in rats fed on diacylglycerol than in those fed on triacylglycerol. In the second trial, varying amounts of dietary triacylglycerol were replaced by diacylglycerol while the dietary fatty acid content was maintained (93.9 g/kg diet). After 21 d of the feeding period the significant reductions in serum and liver triacylglycerol levels were confirmed in groups of rats fed on the diets in which diacylglycerol supplied more than 65.8 g fatty acids/kg diet (65.8 and 93.9 g/kg). Reductions in the activities of enzymes of fatty acid synthesis and increases in palmitoyl-CoA oxidation rates by both mitochondrial and peroxisomal pathways were also apparent when diacylglycerol replaced triacylglycerol in diets to supply more than 65.8 g fatty acid/kg. Increasing dietary levels of diacylglycerol also progressively increased the activities of enzymes involved in the beta-oxidation pathway (carnitine palmitoyltransferase (EC 2.3.1.21), acyl-CoA dehydrogenase (EC 1.3.99.3), acyl-CoA oxidase (EC 1.3.3.6), enoyl-CoA hydratase (EC 4.2.1.17), 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35), 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and delta 3, delta 2-enoyl-CoA isomerase (EC 5.3.3.8)) in the liver. These results suggest that alteration of fatty acid metabolism in the liver is a factor responsible for the serum triacylglycerol-lowering effect of dietary diacylglycerol.
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PMID:Reciprocal responses to dietary diacylglycerol of hepatic enzymes of fatty acid synthesis and oxidation in the rat. 905 34

Two forms of rat peroxisomal acyl-CoA oxidase (ACO-I and -II) interact with the substrate analogs, 3-ketoacyl-CoAs, forming a complex characterized by the so-called charge-transfer (CT) band around 575 nm in the absorption spectra. The CT band of ACO-I exhibited a broad dependency on the acyl chain-length from C4 to C16, whereas that of ACO-II showed increased intensity with a longer acyl chain to reach a maximum with a chain-length of C12. These chain-length dependencies of the CT bands were compared with those of the enzymatic activities reported previously [Setoyama et al. (1995) Biochem. Biophys. Res. Commun. 217, 482-487]. The differences in spectroscopic and enzymatic properties between ACO-I and -II suggest that the amino acid stretch corresponding to the third exon in the ACO sequence affects the binding of the ligand and substrate, since the difference in the primary structure between ACO-I and -II lies in the short amino acid stretch corresponding to the third of the total of 14 exons. On the other hand, resonance Raman spectra of the complexes of ACO-I and -II with 3-ketoacyl-CoAs excited in the CT band showed similar features. The two prominent FAD bands II and III, associated with the C(4a)=N(5) moiety of FAD, were observed at 1,577 and 1,545 cm(-1), respectively. In contrast, the bands at 1,615 and 1,493 cm(-1) in the ACO-I x 3-keto-C8-CoA complex were assigned to the stretching modes of C=O at positions 3 and 1 of the ligand, respectively, by using the isotopically labeled ligands. Both C=O stretching bands were shifted to lower wave numbers upon complex formation with ACO-I, implying that the C=O bond involves the single bond (C-O-) character in the active site cavity. The downshift of the C(1)=O stretching band was larger than that of the C(3)=O stretching band. Therefore, the ligand lies in the active site as the anionic form with a major contribution from C(1)-O-. These observations demonstrate that the CT band around 575 nm arises from the charge-transfer interaction between the oxidized FAD and the enolate transformed after the elimination of the a-proton. The band II of FAD in the complexes reveals a significant decrease in the frequency in comparison with the complexes of medium-chain acyl-CoA dehydrogenase (MCAD) with 3-ketoacyl-CoA. This observation suggests a difference between ACO and MCAD in the hydrogen-bonding network associated with enzyme-bound FAD.
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PMID:Spectroscopic studies of rat liver acyl-CoA oxidase with reference to recognition and activation of substrate. 935 89

Galactomyces reessii accomplishes the enzymatic transformation of beta-methylbutyric acid (isovaleric acid) to beta-hydroxy-beta-methylbutyric acid. The enzymatic basis for this bioconversion was evaluated by analyzing cell-free extracts of G. reessii for enzyme activities commonly associated with leucine catabolism. G. reessii extracts contained activities for acyl-CoA synthetase, acyl-CoA dehydrogenase, and enoyl-CoA hydratase, whereas beta-methylbutyric acid hydroxylase, alpha-ketoisocaproate oxygenase, and acyl-CoA oxidase (with isovaleryl-CoA as substrate) were not observed. Furthermore, beta-methylbutyric acid is initially activated to isovaleryl-CoA by acyl-CoA synthetase, dehydrogenated to methylcrotonyl-CoA by acyl-CoA dehydrogenase, hydrated to beta-hydroxy-beta-methylbutyric acid-CoA by enoyl-CoA hydratase, and hydrolyzed to beta-hydroxy-beta-methylbutyric acid in G. reessii extracts. Cell-free extracts converted both isovaleryl-CoA and methylcrotonyl-CoA into beta-hydroxy-beta-methylbutyric acid, thus demonstrating that beta-methylbutyric acid is part of the leucine catabolic pathway. The rate of beta-methylbutyric acid conversion to beta-hydroxy-beta-methylbutyric acid with cell-free extract was 0. 013 &mgr;mol beta-hydroxy-beta-methylbutyric acid (mg protein)-1 h-1, while the conversion rate of leucine was fivefold lower. With whole cells, the highest production rate [0.042 &mgr;mol beta-hydroxy-beta-methylbutyric acid (g cells)-1 h-1] was also observed with beta-methylbutyric acid. The results indicate that beta-methylbutyric acid is transformed to beta-hydroxy-beta-methylbutyric acid through the leucine catabolic pathway.
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PMID:Enzyme analyses demonstrate that beta-methylbutyric acid is converted to beta-hydroxy-beta-methylbutyric acid via the leucine catabolic pathway by galactomyces reessii 947 61

A range of 4-thiaacyl-CoA derivatives has been synthesized to study the bioactivation of cytotoxic fatty acids by the mitochondrial medium-chain acyl-CoA dehydrogenase and the peroxisomal acyl-CoA oxidase. Both enzymes catalyze alpha-proton abstraction from normal acyl-CoA substrates with elimination of a beta-hydride equivalent to the FAD prosthetic group. In competition with this oxidation reaction, 4-thiaacyl-CoA thioesters undergo dehydrogenase-catalyzed beta-elimination, providing that the corresponding thiolates are sufficiently good leaving groups and can be accommodated by the active site of the enzyme. Thus, the dehydrogenase catalyzes the elimination of 2-mercaptobenzothiazole and 4-nitrothiophenolate from 4-(2-benzothiazole)-4-thiabutanoyl-CoA and 4-(4-nitrophenyl)-4-thiabutanoyl-CoA, respectively. However, the 2,4-dinitrophenyl-analogue appears too bulky and the unsubstituted thiophenyl-derivative is insufficiently activated for significant elimination. Molecular modeling shows that steric interference from the flavin ring dictates a syn rather than an anti elimination. Acryloyl-CoA, the other product of 4-thiaacyl-CoA elimination reactions, is not a significant inactivator of the medium-chain dehydrogenase. In contrast, the irreversible inactivation observed during beta-elimination using 5,6-dichloro-4-thia-5-hexenoyl-CoA (DCTH-CoA), 5,6-dichloro-7,7,7-trifluoro-4-thia-5-heptenoyl-CoA (DCTFTH-CoA), and 6-chloro-5,5,6-trifluoro-4-thiahexanoyl-CoA (CTFTH-CoA) is caused by release of cytotoxic thiolate products within the active site of the dehydrogenase. The double bond between C5 and C6 found in the vinylic analogues DCTH- and DCTFTH-CoA is not essential for enzyme inactivation, although CTFTH-CoA is a weaker inhibitor of the dehydrogenase. Mechanism-based inactivation with CTFTH-CoA requires elimination, is unaffected by exogenous nucleophiles, and is strongly protected by octanoyl-CoA. The peroxisomal acyl-CoA oxidase efficiently oxidizes 4-thiaacyl-CoA analogues, but is only rapidly inactivated by DCTFTH-CoA. The variable ratio of elimination to oxidation observed for DCTH-, DCTFTH-, and CTFTH-CoA may influence the metabolism of the corresponding cytotoxic alkanoic acids in vivo.
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PMID:Elimination reactions in the medium-chain acyl-CoA dehydrogenase: bioactivation of cytotoxic 4-thiaalkanoic acids. 947 67

The acyl-CoA dehydrogenases are a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. Long chain acyl-CoA dehydrogenase (LCAD) and short/branched chain acyl-CoA dehydrogenase (SBCAD) have been shown to have activity towards 2-methyl branched chain acyl-CoA substrates of varying chain lengths. In humans, long chain 2-branched chain fatty acids such as pristanic acid are largely thought to be metabolized in peroxisomes through desaturation of their CoA esters by branched chain acyl-CoA oxidase, but LCAD is also capable of utilizing 2-methyldecanoyl- and 2-methylpalmitoyl-CoA as substrate [1]. Since the acyl-CoA oxidase reaction is specific for the S-enantiomer of the branched chain substrates, we investigated the stereo specificity of mitochondrial LCAD. Purified LCAD had a specific activity of 390 and 340 mU/mg of purified LCAD protein using palmitoyl-CoA and S-2-methylpentadecanoyl-CoA, respectively, as substrate. No activity was measurable with R-2-methylpentadecanoyl-CoA. Purified medium chain acyl-CoA dehydrogenase (MCAD) could also utilize S-2-methylpentadecanoyl-CoA as a substrate, but not R-2-methylpentadecanoyl-CoA. These results indicate that LCAD and MCAD are specific for the S-enantiomers of methylbranched chain substrates. Crude mitochondrial extracts showed no activity when dehydrogenating activity was measured with R/S-2-methylpalmitoyl-CoA or S-2-methylpentadecanoyl-CoA after inactivation of the extract with antibodies to very long chain acyl-CoA dehydrogenase and MCAD, suggesting that this substrate is not useful in identifyig clinical deficiencies of LCAD.
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PMID:Human long chain, very long chain and medium chain acyl-CoA dehydrogenases are specific for the S-enantiomer of 2- methylpentadecanoyl-CoA. 948 54

It has been reported that both n-3 and n-6 octadecatrienoic acids can increase hepatic fatty acid oxidation activity. It remains unclear, however, whether different enzymes in fatty acid oxidation show a similar response to n-3 and n-6 octadecatrienoic acids. The activity of hepatic fatty acid oxidation enzymes in rats fed an oil mixture rich in alpha-linolenic acid (18:3n-3) and borage oil rich in gamma-linolenic acid (18:3n-6) was therefore compared to that in rats fed an oil mixture rich in linoleic acid (18:2n-6) and a saturated fat (palm oil) in this study. Linseed oil served as the source of 18:3n-3 for the oil mixture rich in this octadecatrienoic acid and contained 30.6% 18:3n-3 but not 18:3n-6. Borage oil contained 25.7% 18:3n-6 and 4.5% 18:3n-3. Groups of seven rats each were fed diets containing 15% various fats for 15 d. The oxidation rate of palmitoyl-CoA in the peroxisomes was higher in rats fed a fat mixture rich in 18:3n-3 (3.03 nmol/min/mg protein) and borage oil (2.89 nmol/min/mg protein) than in rats fed palm oil (2.08 nmol/min/mg protein) and a fat mixture rich in 18:2n-6 (2.15 nmol/min/mg protein). The mitochondrial palmitoyl-CoA oxidation rate was highest in rats fed a fat mixture rich in 18:3n-3 (1.93 nmol/min/mg protein), but no significant differences in this parameter were seen among the other groups (1.25-1.46 nmol/min/mg protein). Compared to palm oil and fat mixtures rich in 18:2n-6, a fat mixture rich in 18:3n-3 and borage oil significantly increased the hepatic activity of carnitine palmitoyltransferase and acyl-CoA oxidase. Compared to palm oil and a fat mixture rich in 18:2n-6, a fat mixture rich in 18:3n-3, but not fats rich in 18:3n-6, significantly decreased 3-hydroxyacyl-CoA dehydrogenase activity. Compared to palm oil and a fat mixture rich in 18:2n-6, borage oil profoundly decreased mitochondrial acyl-CoA dehydrogenase activity, but a fat mixture rich in 18:3n-3 increased it. 2,4-Dienoyl-CoA reductase activity was significantly lower in rats fed palm oil than in other groups. Compared to other fats, borage oil significantly increased delt3,delta2-enoyl-CoA isomerase activity. Activity was also significantly higher in rats fed 18:2n-6 oil than in those fed palm oil. It was confirmed that both dietary 18:3n-6 and 18:3n-3 increased fatty acid oxidation activity in the liver. These two dietary octadecatrienoic acids differ considerably, however, in how they affect individual fatty acid oxidation enzymes.
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PMID:Comparative effects of alpha- and gamma-linolenic acids on rat liver fatty acid oxidation. 968 66

Sponges (Porifera) are the phylogenetically oldest metazoan organisms. From one member of the siliceous sponges, Geodia cydonium, the cDNA encoding a putative SOS protein, the AidB-like protein of the Ada system from bacteria, was isolated and characterized. The cDNA, GCaidB, comprises an open reading frame of 446 amino acid (aa) residues encoding a polypeptide with a calculated Mr of 49,335. This molecule shows high similarity to the bacterial AidB proteins from Mycobacterium tuberculosis and Escherichia coli and somewhat lower similarities to acyl-CoA dehydrogenases (ADHs) and acyl-CoA oxidases (AOXs). Northern blot analysis confirmed the presence of the complete transcript. The deduced sponge aa sequence, GC_aidB, possesses the two characteristic acyl-CoA dehydrogenase signatures 1 and 2. Incubation of the sponge with N-methyl-N'-nitro-N-nitrosoguanidine causes a strong increase in the 2.1-kb large transcript of GCaidB; maximal expression is seen after 24 h of incubation with this DNA methylating agent. ADHs and AOXs can be grouped, depending on the position of the catalytically important Glu residue, into the Glu-Gly (Glu adjacent to Gly) class and the Glu-Arg (Glu adjacent to Arg) class. The phylogenetically oldest metazoan AidB-like molecule, GC_aidB of G. cydonium, belongs to the Glu-Gly class of ADHs. Phylogenetic analyses of the Glu-Gly class enzymes, with the described AidB-like protein from G. cydonium and the bacterial AidB polypeptides, together with metazoan ADHs and AOXs, revealed that the AidB(-like) proteins diverged first from a common ancestor, while the eukaryotic AOX and ADA polypeptides as well as the GHDs appeared later. According to the analyses, the very long-chain ADHs are older than the medium-chain, short-chain, and branched-chain ADHs. Inclusion of the phylogenetical oldest member of the Glu-Arg class of enzymes, the bacterial ADH-CaiA sequence in these analyses, revealed that this class of enzymes appeared later in evolution and arose from the Glu-Gly class perhaps after gene duplication.
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PMID:Identification and expression of the SOS response, aidB-like, gene in the marine sponge Geodia cydonium: implication for the phylogenetic relationships of metazoan acyl-CoA dehydrogenases and acyl-CoA oxidases. 973 61

The activities of hepatic enzymes involved in fatty acid synthesis and oxidation were compared in rats fed diets containing different proportions of dried powder of the brown seaweed, Undaria pinnatifida (wakame). Rats were fed diets containing 0, 0.5, 1.0, 2. 0, 5.0 and 10 g/100 g of dried wakame powder. Experimental diets were adjusted to provide consistent amounts of most nutrients, but mineral concentrations were not standardized. After the 21-d feeding period, serum and liver triacylglycerol levels in rats fed diets in which wakame constituted at least 2% were significantly lower than those in rats fed the control diet. The activity of glucose-6-phosphate dehydrogenase was significantly lower in rats fed the 5 and 10% wakame diets than in rats fed the control diet. In contrast, 10% wakame diet increased activities of enzymes involved in the beta-oxidation pathway including hepatic carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, enoyl-CoA hydratase and 2,4-dienoyl-CoA reductase. Some differences were detected in rats fed 5% wakame as well. These results suggest that alterations of the activities of enzymes involved in fatty acid metabolism in the liver are responsible for the serum triacylglycerol-lowering effect of dietary wakame. Thus, wakame may be useful as a food to prevent hyperlipidemia.
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PMID:Hepatic fatty acid oxidation enzyme activities are stimulated in rats fed the brown seaweed, Undaria pinnatifida (wakame). 991 91


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