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)

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (alpha-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFbeta2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF.
J Mol Med (Berl) 2008 Sep
PMID:Sex-specific pathways in early cardiac response to pressure overload in mice. 1866 44

Reye syndrome is an acute metabolic encephalopathy, largely affecting children and adolescents. In Reye-like syndrome, because of inborn errors of metabolism, hypoglycemia, hypoketonemia, elevated ammonia, and organic aciduria are often evident. It is well-known that fatty-acid oxidation defects can present as Reye-like syndrome. The most commonly diagnosed metabolic disorder in association with Reye syndrome has been medium-chain acyl coenzyme A dehydrogenase deficiency. The present consensus seems to be that Reye syndrome is very rare, and that any child suspected of manifesting this disorder should undergo investigations for inborn errors of metabolism. We recently treated a child with "Reye-like illness" who possibly manifested a long-chain acyl dehydrogenase deficiency, and who had also ingested aspirin. We discuss the possible pathogenesis of the disorder in this child. The end results of mitochondrial dysfunction in Reye syndrome and Reye-like illness may be similar.
Pediatr Neurol 2008 Sep
PMID:Reye syndrome and reye-like syndrome. 1872 66

The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 microg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor alpha (PPARalpha), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These results demonstrate that turbulence of fatty acid beta-oxidation and oxidative stress responses were involved in the PFDoA-induced hepatotoxicity.
Aquat Toxicol 2008 Sep 29
PMID:Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver. 1876 Aug 46

The interactions of acyl-CoA with medium-chain acyl-CoA dehydrogenases (MCADs) reconstituted with artificial FADs-i.e. 8-CN-, 7,8-Cl(2)-, 8-Cl-, 8-OCH(3)- and 8-NH(2)-FAD-were investigated by UV-visible absorption and FT-IR measurements. Although 8-NH(2)-FAD-MCAD did not oxidize acyl-CoA the wavelength of the absorption maximum of the flavin was altered by acyl-CoAs binding. Thus, 8-NH(2)-FAD-MCAD is one of the attractive materials for investigation of enzyme-substrate (ES) interaction in ES complex (the complex of oxidized MCAD with acyl-CoA). FT-IR difference spectra between non-labelled and [1-(13)C]-labelled acyl-CoA free in solution and bound to oxidized 8-NH(2)-FAD-MCAD were obtained. The broad 1668-cm(-1) band of free octanoyl-CoA assigned to the C(1) = O stretching vibration appeared as a sharp signal at 1626 cm(-1) in the case of the complex. The downward shift indicates a large polarization of C(1) = O, and the sharpness suggests that the orientation of the C(1) = O in the active-site cavity is fairly limited. The hydrogen-bond enthalpy change responsible for the polarization on the transfer of the substrate from aqueous solution to the active site of MCAD was estimated to be approximately 15 kcal/mol. The 1626-cm(-1) band is noticeably weakened in the case of acyl-CoA with acyl chains longer than C12 which are poor substrates for MCAD, suggesting that C(1) = O is likely to exist in multiple orientations in the active-site cavity, whence the band becomes obscured. A band identical to that of bound C8-CoA was observed in the case of C4-CoA which is a poor substrate, indicating the strong hydrogen bond at C(1) = O.
J Biochem 2009 Sep
PMID:FT-IR spectroscopic studies on the molecular mechanism for substrate specificity/activation of medium-chain acyl-CoA dehydrogenase. 1947 May 21

We report a perinatal death due to medium-chain acyl-CoA dehydrogenase deficiency, which was referred to the Coroner's Physician as sudden unexplained infant death. Detailed death investigation including the autopsy findings, and newborn biochemical and molecular studies revealed the cause and natural manner of death. This disorder affects fatty acid oxidation and results in decreased tolerance for fasting, which can be life threatening. This case illustrates the critical role of newborn screening in the investigation of perinatal death. A brief historical perspective of the origins of newborn biochemical screening is also presented.
Am J Forensic Med Pathol 2009 Sep
PMID:A neonatal death due to medium-chain acyl-CoA dehydrogenase deficiency: utilization of the neonatal metabolic screen in a functional approach to sudden unexplained infant death. 1969 88

We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12 years and 11 months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5 months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD.
Brain Dev 2010 Sep
PMID:Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. 1978 11

Body-weight differences in animals may be ascribed to genetic and environmental factors. Here we utilized two divergent porcine genotypes, the highly muscled, leaner PietrianxYorkshire pigs and less muscled, fatter DurocxYorkshire growing pigs (75-110 kg), to examine the role of genetic background on expression of genes associated with anabolic (Fatty acid synthase, FAS; glucose transporter 4, GLUT-4; stearoyl CoA desaturase, SCD; Sterol regulatory binding protein-1, SREBP-1; leptin) and catabolic lipid metabolism (Carnitine palmitoyltransferase-1B, CPT-1B; acyl-CoA dehydrogenase, ACDH) in adipose tissue (AT), liver (L) and skeletal muscle (SKM). Pietrain pigs had lower mRNA abundance for FAS, SREBP-1, SCD and leptin in AT and L, but higher mRNA abundance for L ACDH and SKM ACDH and CPT-1B than Durocs. Duroc pigs exhibited higher expression of FAS, SREBP-1, SCD, leptin in AT and FAS in L and lower expression of ACDH and CPT-1B in L SKM. GLUT-4 expression did not differ in SKM between the two genotypes. Feeding of a beta adrenergic agonist (Paylean) for 52 days lowered expression of lipid anabolic and enhanced lipid catabolic genes expressions similarly in both genotypes. Overall, the lipid metabolism genes differential expression patterns documented here showed that in Pietrain pigs mRNA abundances of synthesis genes were lower and of catabolic genes were higher than in Duroc pigs.
Comp Biochem Physiol Part D Genomics Proteomics 2007 Sep
PMID:Lipid metabolism related gene-expression profiling in liver, skeletal muscle and adipose tissue in crossbred Duroc and Pietrain Pigs. 2048 93

Over the last years acylcarnitines have emerged as important biomarkers for the diagnosis of mitochondrial fatty acid beta-oxidation (mFAO) and branched-chain amino acid oxidation disorders assuming they reflect the potentially toxic acyl-CoA species, accumulating intramitochondrially upstream of the enzyme block. However, the origin of these intermediates still remains poorly understood. A possibility exists that carnitine palmitoyltransferase 2 (CPT2), member of the carnitine shuttle, is involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites. To address this issue, the substrate specificity profile of CPT2 was herein investigated. Saccharomyces cerevisiae homogenates expressing human CPT2 were incubated with saturated and unsaturated C2-C26 acyl-CoAs and branched-chain amino acid oxidation intermediates. The produced acylcarnitines were quantified by ESI-MS/MS. We show that CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters, whereas virtually no activity was found with short- and very long-chain acyl-CoAs or with branched-chain amino acid oxidation intermediates. Trans-2-enoyl-CoA intermediates were also found to be poor substrates for CPT2. Inhibition studies performed revealed that trans-2-C16:1-CoA may act as a competitive inhibitor of CPT2 (K(i) of 18.8 microM). The results obtained clearly demonstrate that CPT2 is able to reverse its physiological mechanism for medium and long-chain acyl-CoAs contributing to the abnormal acylcarnitines profiles characteristic of most mFAO disorders. The finding that trans-2-enoyl-CoAs are poorly handled by CPT2 may explain the absence of trans-2-enoyl-carnitines in the profiles of mitochondrial trifunctional protein deficient patients, the only defect where they accumulate, and the discrepancy between the clinical features of this and other long-chain mFAO disorders such as very long-chain acyl-CoA dehydrogenase deficiency.
Biochim Biophys Acta 2010 Sep
PMID:Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. 2053 56

In traditional Chinese medicine, the flower of Pueraria lobata (Puerariae Flos) has been used in therapy to counteract the problems associated with alcohol drinking and liver injury. In this study, we investigated the hepatoprotective effects and its mechanisms of tectoridin, an isoflavone glycoside from the flower of P. lobata (Willd.) Ohwi. Ethanol (5g/kg) was given orally every 12h for a total of three doses. 1h after the last dose of ethanol, tectoridin (25, 50 and 100mg/kg) was given intragastrically five times in three consecutive days. The mice were sacrificed at 4h after tectoridin treatment. Peroxisome proliferators-activated receptor alpha (PPARalpha), sterol regulatory element-binding protein (SREBP)-1c and their target genes were evaluated by biochemical analysis and quantitative real-time polymerase chain reaction (qPCR). Mitochondria were isolated for the mitochondrial permeability transition (MPT) and membrane potential (DeltaPsi(m)) assay. Acute ethanol exposure resulted in the significant increase of the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) levels and hepatic mitochondria dysfunction shown as the increase of MPT and the decrease of DeltaPsi(m). However, tectoridin treatment dramatically attenuated these effects. In addition, tectoridin remarkably alleviated the over-production of thiobarbituric acid-reactive substance. Furthermore, tectoridin inhibited the decrease of PPARalpha expression and its target genes, including medium-chain acyl-CoA dehydrogenase (MCAD), acyl-CoA oxidase (ACO) and cytochrome P450 4A (CYP 4A) at mRNA and enzyme activity levels. These data showed that tectoridin protected against ethanol-induced liver steatosis mainly through modulating the disturbance of PPARalpha pathway and ameliorating mitochondrial function.
Toxicology 2010 Sep 30
PMID:Tectoridin, an isoflavone glycoside from the flower of Pueraria lobata, prevents acute ethanol-induced liver steatosis in mice. 2063 25

Brown adipose tissue is a highly specialized organ that uses mitochondrial fatty acid oxidation to fuel non-shivering thermogenesis. In mice, mutations in the acyl-CoA dehydrogenase family of fatty acid oxidation genes are associated with sensitivity to cold. Brown adipose tissue function has not previously been characterized in these knockout strains. Short-chain acyl-CoA dehydrogenase (SCAD) deficient mice were found to have increased brown adipose tissue mass as well as modest cardiac hypertrophy. Uncoupling protein-1 was reduced by 70% in brown adipose tissue and this was not due to a change in mitochondrial number, nor was it due to decreased signal transduction through protein kinase A which is known to be a major regulator of uncoupling protein-1 expression. PKA activity and in vitro lipolysis were normal in brown adipose tissue, although in white adipose tissue a modest increase in basal lipolysis was seen in SCAD-/- mice. Finally, an in vivo norepinephrine challenge of brown adipose tissue thermogenesis revealed normal heat production in SCAD-/- mice. These results suggest that reduced brown adipose tissue function is not the major factor causing cold sensitivity in acyl-CoA dehydrogenase knockout strains. We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved.
Biochem Biophys Res Commun 2010 Sep 24
PMID:Brown adipose tissue function in short-chain acyl-CoA dehydrogenase deficient mice. 2072 52


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