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)

Immunocytochemical localization of delta 3, delta 2-enoyl-CoA isomerase (isomerase) was investigated in rat liver. Livers of di-(2-ethylhexyl)phthalate (DEHP)-treated or untreated rats were perfusion-fixed and embedded in Epon or Lowicryl K4M. By light microscopy, reaction deposits for the enzyme were present in the cytoplasmic granules of hepatocytes and interlobular bile duct epithelium. Weak staining was noted in sinus-lining cells. After administration of DEHP, the granular staining of the hepatocytes was markedly enhanced, whereas the staining reaction of the sinus-lining cells decreased. The isomerase staining pattern was quite similar to that of long-chain acyl-CoA dehydrogenase (a mitochondrial marker), but different from that of catalase (a peroxisomal marker). Under electron microscopy, gold particles for isomerase were seen to be confined mainly to mitochondria of the hepatocytes, the bile duct epithelial cells and sinus-lining cells. Peroxisomes were weakly labeled. After DEHP administration, the peroxisomes were markedly induced, but the mitochondria were not. Quantitative analysis showed that the induction of the peroxisomal isomerase was only 2-fold whereas the mitochondrial isomerase was enhanced about 5-fold, 40 times as high as the peroxisomal enzyme. The results show that the mitochondria are the main intracellular site for isomerase and the peroxisomes a minor site. The mitochondrial isomerase of the rat liver is markedly induced by peroxisome proliferators, DEHP and clofibrate.
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PMID:Immunocytochemical localization of delta 3, delta 2-enoyl-CoA isomerase in rat liver. The effects of di-(2-ethylhexyl)phthalate, a peroxisome proliferator. 260 71

Evidence is presented that Saccharomyces cerevisiae can metabolize fatty acids via the inducible peroxisomal beta-oxidation pathway even when these acids are not the sole carbon source. The fatty acids of chain length of C10-C18 induce acyl-CoA oxidase simultaneously with catalase A but have no effect on catalase T and acyl-CoA dehydrogenase. The coinduction of both acyl-CoA oxidase and catalase A is recorded in strains with both active catalase A and T or displaying only catalase A activity. In mutants lacking catalase A, the induction of acyl-CoA oxidase is observed without a concomitant increase in catalase activity. After centrifugation in a linear Ficoll gradient of the particulate fraction from the cells grown on ethanol and oleate the activity of acyl-CoA oxidase cosediments with catalase A. The relationship of catalase A to acyl-CoA oxidase is discussed.
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PMID:Study of the coinduction by fatty acids of catalase A and acyl-CoA oxidase in standard and mutant Saccharomyces cerevisiae strains. 328 21

Microbodies from rat liver and a variety of plant tissues were osmotically shocked and subsequently centrifuged at 40,000 g for 30 min to yield supernatant and pellet fractions. From rat liver microbodies, all of the uricase activity but little glycolate oxidase or catalase activity were recovered in the pellet, which probably contained the crystalline cores as many other reports had shown. All the measured enzymes in spinach leaf microbodies were solubilized. With microbodies from potato tuber, further sucrose gradient centrifugation of the pellet yielded a fraction at density 1.28 g/cm(3) which, presumably representing the crystalline cores, contained 7% of the total catalase activity but no uricase or glycolate oxidase activity. Using microbodies from castor bean endosperm (glyoxysomes), 50-60% of the malate dehydrogenase, fatty acyl CoA dehydrogenase, and crotonase and 90% of the malate synthetase and citrate synthetase were recovered in the pellet, which also contained 96% of the radioactivity when lecithin in the glyoxysomal membrane had been labeled by previous treatment of the tissue with [(14)C]choline. When the labeled pellet was centrifuged to equilibrium on a sucrose gradient, all the radioactivity, protein, and enzyme activities were recovered together at peak density 1.21-1.22 g/cm(3), whereas the original glyoxysomes appeared at density 1.24 g/cm(3). Electron microscopy showed that the fraction at 1.21-1.22 g/cm(3) was comprised of intact glyoxysomal membranes. All of the membrane-bound enzymes were stripped off with 0.15 M KCl, leaving the "ghosts" still intact as revealed by electron microscopy and sucrose gradient centrifugation. It is concluded that the crystalline cores of plant microbodies contain no uricase and are not particularly enriched with catalase. Some of the enzymes in glyoxysomes are associated with the membranes and this probably has functional significance.
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PMID:Localization of enzymes within microbodies. 472 5

The association of liver peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) with the synthesis of bile acids was investigated. When rats were given clofibrate, a peroxisome proliferator and stimulator of peroxisomal FAOS, the biosynthesis of bile acids was significantly increased. Di(2-ethylhexyl)phthalate, another peroxisome proliferator, also increased the biosynthesis of bile acids. On the other hand, administration of orotate, an inhibitor of mitochondrial FAOS activity, did not affect the biosynthesis. It is known that fatty acyl-CoA oxidase [EC 1.3.99.3] in peroxisomal FAOS conjugates with catalase [EC 1.11.1.6]. When the catalase activity of liver peroxisomes was irreversibly inhibited by administration of 3-amino-1,2,4-triazole (amino-triazole), the biosynthesis of bile acids was suppressed to about one-third, and the serum cholesterol level was increased. However, the bile acid components of the bile obtained from aminotriazole-treated rats were not essentially different from those of control rats, and no accumulation of intermediates of bile acid synthesis was found in this experiment. Peroxisomal FAOS activity of the liver from amino-triazole-treated rats was considerably lower than that of control liver. The above results indicate that liver peroxisomes play a role in the biosynthesis of bile acids in vivo.
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PMID:Association of the liver peroxisomal fatty acyl-CoA beta-oxidation system with the synthesis of bile acids. 653 Mar 93

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

NMRI mice were fed diets supplemented with 0.05, 0.2, or 2% (w/w) docosahexaenoic acid (DHA), a polyunsaturated fatty acid present in fish oil, for 3 d, 3 wk, or 3 mon. The doses of DHA were chosen to supply the mice with concentrations of DHA which approximate those that have been reported to be beneficial to patients with peroxisomal disease. Diets containing 0.05 or 0.2% DHA did not change hepatic, myocardial, and renal catalase (EC 1.11.1.6) activity except for a slight but significant increase (to 120%) in myocardial catalase activity in mice treated with the 0.05% DHA diet for 3 mon. A diet with 2% DHA induced myocardial catalase activity to 150% after both 3 d and 3 wk of administration. In the liver of mice fed this diet for 3 wk, hepatic catalase activity was increased to 140% while no induction of palmitoyl-CoA oxidase (EC 1.3.99.3), urate oxidase (EC 1.7.3.3), and L-alpha-hydroxyisovalerate oxidase (EC 1.1.3.a) was observed. With the light microscope, no changes in peroxisomal morphology were visually evaluated in catalase stained sections of liver, myocardium, and kidney of mice fed either diet. Our results show that in healthy mice a low dietary DHA dose (< 0.2%; this corresponds to a dose prescribed to peroxisomal patients) has no effect on several hepatic peroxisomal H2O2-producing enzymes, including the rate-limiting enzyme of the peroxisomal fatty acid beta-oxidation. This may indicate that such a DHA dose will not add a strong load on the often disturbed fatty acid metabolism in the liver of patients with peroxisomal disorders.
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PMID:Dietary docosahexaenoic acid has little effect on peroxisomes in healthy mice. 893 48

We have previously demonstrated that octanoic (OA) and decanoic acids (DA) inhibit Na+, K+ ATPase activity in synaptic plasma membranes from rat brain. The objective of the present study was to investigate the in vitro effects of the other metabolites that accumulate in tissues of medium-chain acyl-CoA dehydrogenase (MCAD)-deficient patients, namely cis-4-decenoic acid (cDA), octanoylcarnitine (OC), hexanoylcarnitine (HC), hexanoylglycine (HG), phenylpropionylglycine (PPG) and suberoylglycine (SG), on Na+, K+ ATPase activity in synaptic plasma membrane from cerebral cortex of 30-day-old rats. cDA, the pathognomonic compound found in this disorder, provoked the strongest inhibition on this enzyme activity at concentrations as low as 0.25 mM, whereas OC inhibited this activity at 1.0 mM and higher concentrations in a dose-dependent manner. In contrast, HC, HG, PPG and SG did not affect Na+, K+ ATPase activity. Furthermore, pre-treatment of cortical homogenates with the antioxidant enzymes catalase plus superoxide dismutase totally prevented cDA-induced Na+, K+ ATPase inhibition. We also provided evidence that cDA, as well as OA and DA, caused lipid peroxidation, which may explain, at least in part, the inhibitory properties of these compounds towards Na+, K+ ATPase. Considering that Na+, K+ ATPase is a critical enzyme for normal brain development and functioning, it is presumed that these findings, especially those regarding to the marked inhibitory effect of cDA, may be involved in the pathophysiology of the neurological dysfunction of MCAD-deficient patients.
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PMID:Na+, K+ ATPase activity is markedly reduced by cis-4-decenoic acid in synaptic plasma membranes from cerebral cortex of rats. 1620

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased. We previously evaluated the expression of fatty acid metabolism-related genes in NAFLD and reported changes in expression that could contribute to increased fatty acid synthesis. In the present study, we evaluated the expression of additional fatty acid metabolism-related genes in larger groups of NAFLD (n=26) and normal liver (n=10) samples. The target genes for real-time PCR analysis were as follows: acetyl-CoA carboxylase (ACC) 1, ACC2, fatty acid synthase (FAS), sterol regulatory element-binding protein 1c (SREBP-1c), and adipose differentiation-related protein (ADRP) for evaluation of de novo synthesis and uptake of fatty acids; carnitine palmitoyltransferase 1a; (CPT1a), long-chain acyl-CoA dehydrogenase (LCAD), long-chain L-3-hydroxyacylcoenzyme A dehydrogenase alpha (HADHalpha), uncoupling protein 2 (UCP2), straight-chain acyl-CoA oxidase (ACOX), branched-chain acyl-CoA oxidase (BOX), cytochrome P450 2E1 (CYP2E1), CYP4A11, and peroxisome proliferator-activated receptor (PPAR)alpha for oxidation in the mitochondria, peroxisomes and microsomes; superoxide dismutase (SOD), catalase, and glutathione synthetase (GSS) for antioxidant pathways; and diacylglycerol O-acyltransferase 1 (DGAT1), PPARgamma, and hormone-sensitive lipase (HSL) for triglyceride synthesis and catalysis. In NAFLD, although fatty acids accumulated in hepatocytes, their de novo synthesis and uptake were up-regulated in association with increased expression of ACC1, FAS, SREBP-1c, and ADRP. Fatty acid oxidation-related genes, LCAD, HADHalpha, UCP2, ACOX, BOX, CYP2E1, and CYP4A11, were all overexpressed, indicating that oxidation was enhanced in NAFLD, whereas the expression of CTP1a and PPARalpha was decreased. Furthermore, SOD and catalase were also overexpressed, indicating that antioxidant pathways are activated to neutralize reactive oxygen species (ROS), which are overproduced during oxidative processes. The expression of DGAT1 was up-regulated without increased PPARgamma expression, whereas the expression of HSL was decreased. Our data indicated the following regarding NAFLD: i) increased de novo synthesis and uptake of fatty acids lead to further fatty acid accumulation in hepatocytes; ii) mitochondrial fatty acid oxidation is decreased or fully activated; iii) in order to complement the function of mitochondria (beta-oxidation), peroxisomal (beta-oxidation) and microsomal (omega-oxidation) oxidation is up-regulated to decrease fatty acid accumulation; iv) antioxidant pathways including SOD and catalase are enhanced to neutralize ROS overproduced during mitochondrial, peroxisomal, and microsomal oxidation; and v) lipid droplet formation is enhanced due to increased DGAT expression and decreased HSL expression. Further studies will be needed to clarify how fatty acid synthesis is increased by SREBP-1c, which is under the control of insulin and AMP-activated protein kinase.
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PMID:Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. 1767 40

Patients affected by medium-chain acyl-CoA dehydrogenase deficiency (MCADD) suffer from acute episodes of encephalopathy whose underlying mechanisms are poorly known. The present work investigated the in vitro effect of cis-4-decenoic acid (cDA), which accumulates in MCADD, on important parameters of oxidative stress in cerebral cortex of young rats. cDA markedly induced lipid peroxidation, as verified by the increased levels of spontaneous chemiluminescence and thiobarbituric acid-reactive substances. Furthermore, cDA significantly increased carbonyl formation and sulphydryl oxidation, which is indicative of protein oxidative damage, and promoted 2',7'-dihydrodichlorofluorescein oxidation. It was also observed that the non-enzymatic tissue antioxidant defenses were decreased by cDA, whereas the antioxidant enzyme activities catalase, superoxide dismutase and glutathione peroxidase were not altered. Moreover, cDA-induced lipid peroxidation and GSH reduction was totally blocked by free radical scavengers, suggesting that reactive species were involved in these effects. The data indicate that oxidative stress is induced by cDA in rat brain in vitro and that oxidative damage might be involved in the pathophysiology of the encephalopathy in MCADD.
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PMID:Oxidative stress induction by cis-4-decenoic acid: relevance for MCAD deficiency. 1798 55

The content and distribution of body lipids are of special interest for production efficiency and meat quality in the farm animal industry. Triglycerides represent the most variable fraction of tissue lipids, and are mainly stored in adipocytes. Although several studies have reported regional differences in the expression of genes and their products in adipocytes from various species, the characteristics of i.m. adipocytes remain poorly described. To evaluate adipocyte features according to muscle and other fat locations, adipocyte proteins were isolated from trapezius skeletal muscle, and intermuscular, s.c., or perirenal adipose tissues from 6 female pigs (80 d of age). Protein extracts were labeled and analyzed by 2-dimensional, fluorescent, differential gel electrophoresis. The comparisons revealed that 149 spots were always differentially expressed (P < 0.05, ratio exceeding |2|-fold difference) between i.m. adipocytes and the fat cells derived from the 3 other adipose locations. The proteins that were downregulated in i.m. fat cells belonged to various metabolic pathways, such as lipogenesis (cytosolic malate dehydrogenase and isocitrate dehydrogenase, P < 0.01), glycolysis (enolases and aldolase, P </= 0.01), lipolysis (perilipin, P < 0.01), fatty acid oxidation (long-chain fatty-acyl CoA dehydrogenase, P < 0.01), and energy transfer (catalase, voltage-dependent anion channel 1, and electron-transfer flavoprotein, P < 0.05). In contrast, both prohibitin-1 and cell division cycle 42 homolog, with possible roles in cell growth, were up-regulated (P < 0.05) in i.m. adipocytes compared with other fat cells. Fewer differences were observed when adipocytes isolated from s.c., perirenal, and intermuscular fat tissues were compared, with a maximum of 17 spots differing significantly in abundance between perirenal and s.c. adipose tissues. The findings that proteins involved in both anabolic and energy-yielding catabolic pathways are downregulated in i.m. adipocytes compared with s.c., visceral, or intermuscular adipocytes, suggest that the metabolic activity of i.m. adipocytes is low. Thus, triggering adipogenesis rather than cell metabolism per se might be a valuable strategy to control lipid deposition in pig skeletal muscles.
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PMID:Regional differences in porcine adipocytes isolated from skeletal muscle and adipose tissues as identified by a proteomic approach. 1831 Apr 87


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