Genomes and Genes
acyl coa dehydrogenase
Summary: A flavoprotein oxidoreductase that has specificity for medium-chain fatty acids. It forms a complex with ELECTRON TRANSFERRING FLAVOPROTEINS and conveys reducing equivalents to UBIQUINONE.
- Wood P, Amendt B, Rhead W, Millington D, Inoue F, Armstrong D. Short-chain acyl-coenzyme A dehydrogenase deficiency in mice. Pediatr Res. 1989;25:38-43 pubmed..This mouse model presents important opportunities to investigate the biology of mammalian fatty acid metabolism and the related human diseases. ..
- Leonard J, Dezateux C. Newborn screening for medium chain acyl CoA dehydrogenase deficiency. Arch Dis Child. 2009;94:235-8 pubmed publisherMedium chain acyl CoA dehydrogenase deficiency (MCADD) is an uncommon inborn error of fatty acid oxidation that is a preventable cause of morbidity and mortality...
- Derks T, Reijngoud D, Waterham H, Gerver W, van den Berg M, Sauer P, et al. The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr. 2006;148:665-670 pubmed..Strikingly, after the diagnosis and initiation of treatment, overweight and chronic complaints (fatigue, muscle pain, and reduced exercise tolerance) were prominent. ..
- Grosse S, Khoury M, Greene C, Crider K, Pollitt R. The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update. Genet Med. 2006;8:205-12 pubmed..Systematic collection and analysis of follow-up data are still needed to ascertain the frequencies of outcomes in screened cohorts. ..
- O Reilly L, Bross P, Corydon T, Olpin S, Hansen J, Kenney J, et al. The Y42H mutation in medium-chain acyl-CoA dehydrogenase, which is prevalent in babies identified by MS/MS-based newborn screening, is temperature sensitive. Eur J Biochem. 2004;271:4053-63 pubmed..Our study suggests that Y42H is a temperature sensitive mutation, which is mild at low temperatures, but may have deleterious effects at increased temperatures. ..
- Schulze A, Lindner M, Kohlmüller D, Olgemöller K, Mayatepek E, Hoffmann G. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics. 2003;111:1399-406 pubmed..This strategy represents valuable preventive medicine by enabling diagnosis and treatment before the onset of symptoms. ..
- Kuchler B, Abdel Ghany A, Bross P, Nandy A, Rasched I, Ghisla S. Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site. Biochem J. 1999;337 ( Pt 2):225-30 pubmed..7 (T168A-MCADH) and the rates of enzyme flavin reduction (stopped-flow measurements) are only approx. 1/10 those of the parent enzyme. These properties are discussed in the light of the possible mechanisms leading to disease in humans. ..
- Matsubara Y, Kraus J, Ozasa H, Glassberg R, Finocchiaro G, Ikeda Y, et al. Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat liver medium chain acyl coenzyme A dehydrogenase. J Biol Chem. 1987;262:10104-8 pubmed..The sequencing of other homologous acyl-CoA dehydrogenases will be informative in this regard. ..
- Chace D, Hillman S, Van Hove J, Naylor E. Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin Chem. 1997;43:2106-13 pubmed..No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency. ..
- Gregersen N, Andresen B, Bross P. Prevalent mutations in fatty acid oxidation disorders: diagnostic considerations. Eur J Pediatr. 2000;159 Suppl 3:S213-8 pubmed..This is exemplified in disorders of mitochondrial fatty acid oxidation. ..
- Nichols M, Saavedra Matiz C, Pass K, Caggana M. Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985 A > G mutation in the New York state population. Am J Med Genet A. 2008;146A:610-9 pubmed publisher..These results suggest that p.K304E has a far lower representation in New York newborns with MCADD than current literature estimates and its full mutational spectrum is still unknown. ..
- Rhead W. Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: a global perspective. J Inherit Metab Dis. 2006;29:370-7 pubmed..Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, reduces morbidity and mortality, and merits expansion to other populations worldwide. ..
- Satoh A, Nakajima Y, Miyahara I, Hirotsu K, Tanaka T, Nishina Y, et al. Structure of the transition state analog of medium-chain acyl-CoA dehydrogenase. Crystallographic and molecular orbital studies on the charge-transfer complex of medium-chain acyl-CoA dehydrogenase with 3-thiaoctanoyl-CoA. J Biochem. 2003;134:297-304 pubmed..The structure of the highest occupied molecular orbital of the complex revealed the electron flow pathway from a substrate to the flavin ring. ..
- Kelly D, Kim J, Billadello J, Hainline B, Chu T, Strauss A. Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. Proc Natl Acad Sci U S A. 1987;84:4068-72 pubmed..The isolation and characterization of MCAD cDNA is an important step in the definition of the defect underlying MCAD deficiency and in understanding its metabolic consequences. ..
- Yokota I, Indo Y, Coates P, Tanaka K. Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation. J Clin Invest. 1990;86:1000-3 pubmed..Thus, this A----G-985 transition is the single prevalent mutation causing MCAD deficiency, a highly unusual feature for any genetic disorder. The PCR/Nco I digestion method is suitable for the diagnosis of MCAD deficiency. ..
- Duran M, Hofkamp M, Rhead W, Saudubray J, Wadman S. Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency. Pediatrics. 1986;78:1052-7 pubmed..Careful monitoring of at-risk patients during a minor illness is necessary. ..
- Tolwani R, Farmer S, Wood P. Molecular cloning and characterization of the mouse medium-chain acyl-CoA dehydrogenase cDNA. Genomics. 1994;23:247-9 pubmed..Amino acid residues where substitutions result in human MCAD deficiency are conserved in the mouse. Amino acid residues involved in important enzymatic functions are also conserved. ..
- Tolwani R, Farmer S, Johnson K, Davisson M, Kurtz D, Hinsdale M, et al. Structure and chromosomal location of the mouse medium-chain acyl-CoA dehydrogenase-encoding gene and its promoter. Gene. 1996;170:165-71 pubmed..Chem. 268 (1993) 13805-13810]. We have mapped mouse Acadm to the distal end of chromosome 3. Sequences previously localized to chromosome 8 are shown to be a pseudogene, and an additional pseudogene was identified on chromosome 11. ..
- Feillet F, Steinmann G, Vianey Saban C, de Chillou C, Sadoul N, Lefebvre E, et al. Adult presentation of MCAD deficiency revealed by coma and severe arrythmias. Intensive Care Med. 2003;29:1594-7 pubmed..This is one of only a few reports of severe cardiac arrhythmia in an adult due to MCAD deficiency. This condition is probably under-diagnosed in adult patients with acute neurological and/or cardiac presentations. ..
- Maclean K, Rasiah V, Kirk E, Carpenter K, Cooper S, Lui K, et al. Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. Acta Paediatr. 2005;94:114-6 pubmed..Metabolic disorders must be kept in mind as a differential diagnosis in acutely ill infants, but it must also be emphasized that carnitine therapy is not uniformly effective in all MCAD patients. ..
- Waddell L, Wiley V, Carpenter K, Bennetts B, Angel L, Andresen B, et al. Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations. Mol Genet Metab. 2006;87:32-9 pubmed..In the meantime, all MCAD patients identified by newborn screening have, by definition, a functional defect and require careful clinical management. ..
- Honda K, Saneyasu T, Sugimoto H, Kurachi K, Takagi S, Kamisoyama H. Role of peroxisome proliferator-activated receptor alpha in the expression of hepatic fatty acid oxidation-related genes in chickens. Anim Sci J. 2016;87:61-6 pubmed publisher..These results suggest that, unlike in mammals, CPT1a and ACO might play an important role in PPARÎ±-induced fatty acid oxidation in the liver of chickens. ..
- Fukushima A, Alrob O, Zhang L, Wagg C, Altamimi T, Rawat S, et al. Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart. Am J Physiol Heart Circ Physiol. 2016;311:H347-63 pubmed publisher..Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. ..
- Diekman E, de Sain van der Velden M, Waterham H, Kluijtmans L, Schielen P, Van Veen E, et al. The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency. JIMD Rep. 2016;27:101-6 pubmed publisher..Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms. ..
- Wu J, Bell A, Luo L, Stephens A, Stankovich M, Tonge P. Probing hydrogen-bonding interactions in the active site of medium-chain acyl-CoA dehydrogenase using Raman spectroscopy. Biochemistry. 2003;42:11846-56 pubmed
- Arakawa H, Uetanaka K, Maeda M, Tsuji A, Matsubara Y, Narisawa K. Analysis of polymerase chain reaction-product by capillary electrophoresis with laser-induced fluorescence detection and its application to the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency. J Chromatogr A. 1994;680:517-23 pubmed..The mutant allele produced a 175-base pairs DNA fragment, which the normal allele generated a 202-base pairs DNA fragment. CGE-LIF clearly distinguished these PCR products, facilitating rapid diagnosis of MCAD deficiency. ..
- Beresford M, Pourfarzam M, Turnbull D, Davidson J. So doctor, what exactly is wrong with my muscles? Glutaric aciduria type II presenting in a teenager. Neuromuscul Disord. 2006;16:269-73 pubmed..An outline of this rare but important disease, its clinical characteristics and diagnostic methodology are given. ..
- Takusa Y, Yamaguchi S. [Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency]. Nihon Rinsho. 2002;60 Suppl 4:722-5 pubmed
- Eura Y, Ishihara N, Oka T, Mihara K. Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function. J Cell Sci. 2006;119:4913-25 pubmed..Together, these findings suggest that MIB is essential for cellular function by regulating mitochondrial membrane dynamics in cooperation with Mfn proteins. ..
- Saijo T, Kim J, Kuroda Y, Tanaka K. The roles of threonine-136 and glutamate-137 of human medium chain acyl-CoA dehydrogenase in FAD binding and peptide folding using site-directed mutagenesis: creation of an FAD-dependent mutant, T136D. Arch Biochem Biophys. 1998;358:49-57 pubmed..These findings also support the notion that the isoalloxazine ring plays a critical role in the MCAD folding, presumably exerting nucleating effects. ..
- Nishina Y, Sato K, Tamaoki H, Setoyama C, Miura R, Shiga K. FT-IR spectroscopic studies on the molecular mechanism for substrate specificity/activation of medium-chain acyl-CoA dehydrogenase. J Biochem. 2009;146:351-7 pubmed publisher..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. ..
- Ho S, Lukacs Z, Hoffmann G, Lindner M, Wetter T. Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Clin Chem. 2007;53:1330-7 pubmed..Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach. ..
- Joy P, Black C, Rocca A, Haas M, Wilcken B. Neuropsychological functioning in children with medium chain acyl coenzyme a dehydrogenase deficiency (MCADD): the impact of early diagnosis and screening on outcome. Child Neuropsychol. 2009;15:8-20 pubmed publisher..Early diagnosis and greater number of hospitalizations were related to higher verbal, communication, and socialization skills. Overall, our results highlight the importance of early diagnosis and management for children with MCADD. ..
- Okere I, Chandler M, McElfresh T, Rennison J, Kung T, Hoit B, et al. Carnitine palmitoyl transferase-I inhibition is not associated with cardiac hypertrophy in rats fed a high-fat diet. Clin Exp Pharmacol Physiol. 2007;34:113-9 pubmed..5. Taken together, the data suggest that consuming a high-fat diet or inhibiting CPT-I do not result in cardiac hypertrophy or cardiac dysfunction in normal rats. ..
- ..identify a regulatory circuit involving a heat-induced acyl-CoA dehydrogenase that controls the lipid saturation level and the fluidity of cellular membranes by transcriptionally regulating a lipid desaturase. ..
- Jiang X, Wang J, Gao Y, Chan L, Lam P, Gu J. Relationship of proteomic variation and toxin synthesis in the dinoflagellate Alexandrium tamarense CI01 under phosphorus and inorganic nitrogen limitation. Ecotoxicology. 2015;24:1744-53 pubmed publisher..The above findings are in support of our hypothesis that these proteins are involved in toxin biosynthesis of A. tamarense CI01, but cause-and-effect mechanisms need to be investigated in further studies. ..
- Tucci S. Very long-chain acyl-CoA dehydrogenase (VLCAD-) deficiency-studies on treatment effects and long-term outcomes in mouse models. J Inherit Metab Dis. 2017;40:317-323 pubmed publisher..While long term use of MCT oil in mice has adverse effects, no such effects have been demonstrated in humans, likely reflecting the differences in long chain fatty acid oxidation between the two species. ..
- Loeber J. Neonatal screening in Europe; the situation in 2004. J Inherit Metab Dis. 2007;30:430-8 pubmed..The huge difference of recall rates illustrate one obvious and important area for improvement of programme performances that could be aided by strengthened European cooperation. ..
- Bago B, Zipfel W, Williams R, Jun J, Arreola R, Lammers P, et al. Translocation and utilization of fungal storage lipid in the arbuscular mycorrhizal symbiosis. Plant Physiol. 2002;128:108-24 pubmed..We conclude that large amounts of lipid are translocated within the AM fungal colony and that, whereas net movement is from the IRM to the ERM, there is also substantial recirculation throughout the fungus. ..
- Opdal S, Rognum T. The sudden infant death syndrome gene: does it exist?. Pediatrics. 2004;114:e506-12 pubmed
- Campbell J, Cronan J. The enigmatic Escherichia coli fadE gene is yafH. J Bacteriol. 2002;184:3759-64 pubmed..Our prior genome array analyses showed that transcription of the yafH gene is controlled by the FadR regulatory protein. We now report direct experimental proof that yafH and fadE are the same gene. ..
- Peng Y, Zhu M, Zheng J, Zhu Y, Li X, Wei C, et al. Bent spine syndrome as an initial manifestation of late-onset multiple acyl-CoA dehydrogenase deficiency: a case report and literature review. BMC Neurol. 2015;15:114 pubmed publisher..Causative mutations were found in the ETFDH gene. We report the first case of late-onset MADD with sensory neuropathy initially manifesting as bent spine syndrome and dropped head syndrome. ..
- Ørngreen M, Vissing J. Treatment Opportunities in Patients With Metabolic Myopathies. Curr Treat Options Neurol. 2017;19:37 pubmed publisher..Further potential treatment targets are molecular therapies aimed at enzyme correction, such as chaperone therapy, gene therapy, gene expression therapy, and enzyme replacement therapies. ..
- Seki M, Powers J, Maruyama S, Zuriaga M, Wu C, Kurishima C, et al. Acute and Chronic Increases of Circulating FSTL1 Normalize Energy Substrate Metabolism in Pacing-Induced Heart Failure. Circ Heart Fail. 2018;11:e004486 pubmed publisher..These findings support a novel function for FSTL1 and provide the first direct evidence that a circulating cardiokine/myokine can alter myocardial and systemic energy substrate metabolism, in vivo. ..
- Xia X, Huang Y, Xu X. [Epididymal sperm protein P34H and male reproduction]. Zhonghua Nan Ke Xue. 2002;8:356-8, 362 pubmed..This paper reviews the molecular properties and regulation of the expression of P34H and its association with male reproduction. ..
- Finocchiaro G, Ito M, Tanaka K. Purification and properties of short chain acyl-CoA, medium chain acyl-CoA, and isovaleryl-CoA dehydrogenases from human liver. J Biol Chem. 1987;262:7982-9 pubmed..The pattern of substrate specificity for these enzymes determined using ETF as electron acceptor significantly differed from that determined using PMS. All of them were severely inhibited by (methylenecyclopropyl)acetyl-CoA. ..
- Greco D, Kotronen A, Westerbacka J, Puig O, Arkkila P, Kiviluoto T, et al. Gene expression in human NAFLD. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1281-7 pubmed publisher..The data show that multiple changes in gene expression characterize simple steatosis. ..
- Valenciano S, Lucas J, Pedregosa A, Monistrol I, Laborda F. Induction of beta-oxidation enzymes and microbody proliferation in Aspergillus nidulans. Arch Microbiol. 1996;166:336-41 pubmed..Nevertheless, growth on acetate did not cause a massive proliferation of microbodies in A. nidulans. ..
- Garcia Viloca M, Poulsen T, Truhlar D, Gao J. Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction. Protein Sci. 2004;13:2341-54 pubmed..The second case is xylose isomerase, and the chief difference of the two structures appears to be the ligand sphere of a Mg2+ metal cofactor that plays an active role in catalysis. ..
- Ouali F, Djouadi F, Bastin J. Effects of fatty acids on mitochondrial beta-oxidation enzyme gene expression in renal cell lines. Am J Physiol Renal Physiol. 2002;283:F328-34 pubmed
- Ruiz Lozano P, Smith S, Perkins G, Kubalak S, Boss G, Sucov H, et al. Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos. Development. 1998;125:533-44 pubmed..We propose a model whereby defects in intermediary metabolism may be a causative factor of the RXRalpha-/- phenotype and resembles an embryonic form of dilated cardiomyopathy. ..