Genomes and Genes
long chain acyl coa dehydrogenase
Summary: A flavoprotein oxidoreductase that has specificity for long-chain fatty acids. It forms a complex with ELECTRON-TRANSFERRING FLAVOPROTEINS and conveys reducing equivalents to UBIQUINONE.
- Schuler A, Barnes S, Gower B, Wood P. Dietary phytoestrogens increase metabolic resistance (cold tolerance) in long-chain acyl-CoA dehydrogenase-deficient mice. J Nutr. 2004;134:1028-31 pubmed..Furthermore, they suggest changes that could improve pediatric formula constituents, especially with regard to management of children with inborn errors of fatty acid oxidation. ..
- Roe C, Sweetman L, Roe D, David F, Brunengraber H. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. J Clin Invest. 2002;110:259-69 pubmed..There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. ..
- Kurtz D, Rinaldo P, Rhead W, Tian L, Millington D, Vockley J, et al. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A. 1998;95:15592-7 pubmed..Approximately 10% of adult LCAD -/- males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/- mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo. ..
- Tucci S, Primassin S, Spiekerkoetter U. Fasting-induced oxidative stress in very long chain acyl-CoA dehydrogenase-deficient mice. FEBS J. 2010;277:4699-708 pubmed publisher..An MCT diet does not prevent hepatic damage during catabolism and metabolic derangement. ..
- Souri M, Aoyama T, Orii K, Yamaguchi S, Hashimoto T. Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients. Am J Hum Genet. 1996;58:97-106 pubmed..VLCAD activity was not detected in mutants' transfectants. Thus, we verified that all five mutations identified in these four patients were disease-causing alterations. ..
- Yoo J, Cheng O, Gerber G. Determination of the native form of FadD, the Escherichia coli fatty acyl-CoA synthetase, and characterization of limited proteolysis by outer membrane protease OmpT. Biochem J. 2001;360:699-706 pubmed..This suggested that FadD undergoes ligand-induced conformational changes and implies that the region surrounding the cleavage site is mobile, a common characteristic of linker domains. ..
- Brix A, Elgavish A, Nagy T, Gower B, Rhead W, Wood P. Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse. Mol Genet Metab. 2002;75:219-26 pubmed..In summary, despite obese mice having an excess of fat available for mitochondrial beta-oxidation in liver, overall energy balance appeared to dictate that the net liver FAO remained at control levels. ..
- Smelt A, Poorthuis B, Onkenhout W, Scholte H, Andresen B, van Duinen S, et al. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset. Ann Neurol. 1998;43:540-4 pubmed..Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis. ..
- Mahadevan U, Padmanaban G. Cloning and expression of an acyl-CoA dehydrogenase from Mycobacterium tuberculosis. Biochem Biophys Res Commun. 1998;244:893-7 pubmed
- Irie J, Reck B, Wu Y, Wicker L, Howlett S, Rainbow D, et al. Genome-wide microarray expression analysis of CD4+ T Cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes. J Immunol. 2008;180:1071-9 pubmed..These results validate the approach of using congenic mice together with genome-wide analysis of tissue-specific gene expression to identify novel candidate genes in T1D...
- Li H, Fukuda S, Hasegawa Y, Kobayashi H, Purevsuren J, Mushimoto Y, et al. Effect of heat stress and bezafibrate on mitochondrial beta-oxidation: comparison between cultured cells from normal and mitochondrial fatty acid oxidation disorder children using in vitro probe acylcarnitine profiling assay. Brain Dev. 2010;32:362-70 pubmed publisher..Our approach is a simple and promising strategy to evaluate the effects of heat stress or therapeutic drugs on mitochondrial FAO. ..
- Gobin Limballe S, McAndrew R, Djouadi F, Kim J, Bastin J. Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches. Biochim Biophys Acta. 2010;1802:478-84 pubmed publisher..Overall, combination of structural, biochemical, and pharmacological analysis allowed assessment of the relative severity of individual mutations, with possible applications for disease management and therapeutic approach. ..
- Alaygut D, Torun Bayram M, Kasap B, Soylu A, Turkmen M, Kavukcu S. Rhabdomyolysis with different etiologies in childhood. World J Clin Pediatr. 2017;6:161-168 pubmed publisher..It is important to distinguish the sporadic and recurrent rhabdomyolysis cases from each other. Recurrent rhabdomyolysis cases should follow up more regardful and attentive. ..
- Chegary M, te Brinke H, Doolaard M, IJlst L, Wijburg F, Wanders R, et al. Characterization of L-aminocarnitine, an inhibitor of fatty acid oxidation. Mol Genet Metab. 2008;93:403-10 pubmed..Therefore, we conclude that in intact cells L-AC inhibits CPT2. Combined with our observation that l-AC does not activate PPAR, we suggest that L-AC is useful to simulate a FAO defect in cells from different origin. ..
- Carpenter K, Pollitt R, Middleton B. Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria. Biochem Biophys Res Commun. 1992;183:443-8 pubmed..coli, but unique in its membrane location and substrate specificity. We propose that its existence explains the repeated failure to detect any intermediates of mitochondrial beta-oxidation. ..
- Tsygankova P, Zakharova E, Baydakova G. Gene symbol: ACADVL. Disease: Very long chain acyl-CoA dehydrogenase deficiency. Hum Genet. 2008;124:299 pubmed
- Yamamoto S, Ogasawara N, Yamamoto K, Uemura C, Takaya Y, Shiraishi T, et al. Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-?B-mediated cytokine production. Biochem Biophys Res Commun. 2017;483:911-916 pubmed publisher..Thus, CAM suppresses NF-?B-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2. ..
- Ves Losada A, Brenner R. Fatty acid delta 5 desaturation in rat liver cell nuclei. Mol Cell Biochem. 1995;142:163-70 pubmed..This step would be essential in nuclear desaturation since when ATP and/or CoA (necessary for the acylation reaction) are omitted from the incubation mixture, the desaturation reaction does not take place. ..
- Indo Y, Yang Feng T, Glassberg R, Tanaka K. Molecular cloning and nucleotide sequence of cDNAs encoding human long-chain acyl-CoA dehydrogenase and assignment of the location of its gene (ACADL) to chromosome 2. Genomics. 1991;11:609-20 pubmed..4 to 32.7% identical residues with three other human enzymes in the acyl-CoA dehydrogenase family, sharing 57 perfectly conserved residues among them. The human pLCAD gene is assigned to chromosome 2, bands q34-q35. ..
- Aliefendioglu D, Dursun A, Coskun T, Akcoren Z, Wanders R, Waterham H. A newborn with VLCAD deficiency. Clinical, biochemical, and histopathological findings. Eur J Pediatr. 2007;166:1077-80 pubmed..The fatal course of the patient may have resulted from diffuse lipid accumulation in the liver and myocardium, which probably began during the intrauterine life with slight hypoalbuminemia as a silent marker of this process. ..
- Wanders R, Denis S, Ruiter J, Ijlst L, Dacremont G. 2,6-Dimethylheptanoyl-CoA is a specific substrate for long-chain acyl-CoA dehydrogenase (LCAD): evidence for a major role of LCAD in branched-chain fatty acid oxidation. Biochim Biophys Acta. 1998;1393:35-40 pubmed
- Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner M, Boehles H, et al. Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop. J Inherit Metab Dis. 2009;32:498-505 pubmed publisher..On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects. ..
- Primassin S, ter Veld F, Mayatepek E, Spiekerkoetter U. Carnitine supplementation induces acylcarnitine production in tissues of very long-chain acyl-CoA dehydrogenase-deficient mice, without replenishing low free carnitine. Pediatr Res. 2008;63:632-7 pubmed publisher..The principle mechanism regulating carnitine homeostasis seems to be endogenous carnitine biosynthesis, also under conditions with increased demand of carnitine such as in VLCAD-deficiency. ..
- McAndrew R, Wang Y, Mohsen A, He M, Vockley J, KIM J. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J Biol Chem. 2008;283:9435-43 pubmed publisher..VLCAD deficiency is among the more common defects of mitochondrial beta-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype. ..
- Laplante M, Festuccia W, Soucy G, Gélinas Y, Lalonde J, Berger J, et al. Mechanisms of the depot specificity of peroxisome proliferator-activated receptor gamma action on adipose tissue metabolism. Diabetes. 2006;55:2771-8 pubmed
- Indo Y, Coates P, Hale D, Tanaka K. Immunochemical characterization of variant long-chain acyl-CoA dehydrogenase in cultured fibroblasts from nine patients with long-chain acyl-CoA dehydrogenase deficiency. Pediatr Res. 1991;30:211-5 pubmed..If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency. ..
- Touma E, Rashed M, Vianey Saban C, Sakr A, Divry P, Gregersen N, et al. A severe genotype with favourable outcome in very long chain acyl-CoA dehydrogenase deficiency. Arch Dis Child. 2001;84:58-60 pubmed..VLCAD enzyme activity was severely decreased to 2% of control levels. Dietary management consisted of skimmed milk supplemented with medium chain triglycerides and L-carnitine. Outcome was good and there was no acute recurrence. ..
- Wood P, Farmer S, Tolwani R, Warren J, Steinkampf M, Johnson L, et al. Molecular studies of mouse medium and long-chain acyl-CoA dehydrogenase genes for site-directed mutagenesis of embryonic stem cells. Prog Clin Biol Res. 1992;375:151-60 pubmed
- Orii K, Saito Ohara F, Ikeuchi T, Orii T, Kondo N, Aoyama T, et al. Assignment of the gene for very-long-chain acyl-CoA dehydrogenase (Acadvl) to mouse chromosome band 11B2-B5 by in situ hybridization. Cytogenet Cell Genet. 1997;78:25-6 pubmed
- Takusa Y, Fukao T, Kimura M, Uchiyama A, Abo W, Tsuboi Y, et al. Identification and characterization of temperature-sensitive mild mutations in three Japanese patients with nonsevere forms of very-long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2002;75:227-34 pubmed..Expression analysis at 30 degrees C may be more useful for evaluating these missense mutations, compared with that at 37 degrees C. ..
- StÄ™pieÅ„ K, Roberts M, Hendriksz C. Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency--diagnostic difficulties and own experience in multidisciplinary management. Dev Period Med. 2015;19:450-3 pubmed..Hence, the liaison between neurologists, rheumatologists and metabolic physicians is essential in early diagnosis and the management of patients with conditions causing myopathy. ..
- Parini R, Menni F, Garavaglia B, Fesslova V, Melotti D, Massone M, et al. Acute, severe cardiomyopathy as main symptom of late-onset very long-chain acyl-coenzyme A dehydrogenase deficiency. Eur J Pediatr. 1998;157:992-5 pubmed..The clinical course after diagnosis was favourable. late-onset VLCAD deficiency may present as acute cardiomyopathy. ..
- Dyke P, Konczal L, Bartholomew D, McBride K, Hoffman T. Acute dilated cardiomyopathy in a patient with deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. Pediatr Cardiol. 2009;30:523-6 pubmed publisher..This report describes the acute decompensation of a 3-year-old girl who had LCHADD with rapidly developing dilated cardiomyopathy. A review of the literature and possible causes of cardiomyopathy in LCHADD are explored. ..
- Olpin S, Clark S, Andresen B, Bischoff C, Olsen R, Gregersen N, et al. Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency. J Inherit Metab Dis. 2005;28:533-44 pubmed..The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed. ..
- Ikeda Y, Tanaka K. Selective inactivation of various acyl-CoA dehydrogenases by (methylenecyclopropyl)acetyl-CoA. Biochim Biophys Acta. 1990;1038:216-21 pubmed..1981) J. Biol. Chem. 256, 9809-9812). Spectrophotometric titration data of LCADH and MCPA-CoA is typical of non-reacting CoA ester. ..
- Welsink Karssies M, Polderman J, Nieveen van Dijkum E, Preckel B, Schlack W, Visser G, et al. Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency and Perioperative Management in Adult Patients. JIMD Rep. 2017;34:49-54 pubmed publisher..The patient was monitored with a continuous glucose meter and creatinine kinase measurements. ..
- Amorim P, Nguyen T, Shingu Y, Schwarzer M, Mohr F, Schrepper A, et al. Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression. J Thorac Cardiovasc Surg. 2010;140:1160-7 pubmed publisher..Mitochondrial dysfunction was characterized by a reduced capacity to oxidize fatty acids and might have resulted from impaired mitochondrial biogenesis through the lack of p38 mitogen-activated protein kinase. ..
- Ji H, Friedman M. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity. Metabolism. 2007;56:1124-30 pubmed..These findings provide a metabolic mechanism for the development of diet-induced obesity and thus suggest potential targets for intervention strategies to treat or prevent it. ..
- Yu H, Wang B, Zhao J, Yao X, Gu Y, Li Y. Protective effect of bicyclol on tetracycline-induced fatty liver in mice. Toxicology. 2009;261:112-8 pubmed publisher..Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARalpha pathway and ameliorating mitochondrial function. ..
- Clark Taylor T, Clark Taylor B. Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase. Med Hypotheses. 2004;62:970-5 pubmed..It is hypothesized that LCAD deficiency may be a cause of autism. Similarities between metabolic disturbances in autism, and those of disorders of fatty acid beta-oxidation are discussed. ..
- Merritt J, Nguyen T, Daniels J, Matern D, Schowalter D. Biochemical correction of very long-chain acyl-CoA dehydrogenase deficiency following adeno-associated virus gene therapy. Mol Ther. 2009;17:425-9 pubmed publisher..This demonstrates the ability of human VLCAD to correct the biochemical phenotype of VLCAD-deficient mice. ..
- Skilling H, Coen P, Fairfull L, Ferrell R, Goodpaster B, Vockley J, et al. Brown adipose tissue function in short-chain acyl-CoA dehydrogenase deficient mice. Biochem Biophys Res Commun. 2010;400:318-22 pubmed publisher..We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved. ..
- ter Veld F, Primassin S, Hoffmann L, Mayatepek E, Spiekerkoetter U. Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice. J Lipid Res. 2009;50:1556-62 pubmed publisher..This is the first study demonstrating that acylcarnitines and acyl-CoA directly correlate and concomitantly increase after exercise in VLCAD-deficient muscle. ..
- Mathur A, Sims H, Gopalakrishnan D, Gibson B, Rinaldo P, Vockley J, et al. Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation. 1999;99:1337-43 pubmed..Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible. ..
- Liang X, Le W, Zhang D, Schulz H. Impact of the intramitochondrial enzyme organization on fatty acid oxidation. Biochem Soc Trans. 2001;29:279-82 pubmed..Altogether, a view is emerging of the organization of beta-oxidation enzymes in mitochondria that supports the idea of intermediate channelling and explains the apparent absence of true intermediates of beta-oxidation from mitochondria. ..
- Shigematsu Y, Hirano S, Hata I, Tanaka Y, Sudo M, Tajima T, et al. Selective screening for fatty acid oxidation disorders by tandem mass spectrometry: difficulties in practical discrimination. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;792:63-72 pubmed
- Djouadi F, Aubey F, Schlemmer D, Gobin S, Laforet P, Wanders R, et al. Potential of fibrates in the treatment of fatty acid oxidation disorders: revival of classical drugs?. J Inherit Metab Dis. 2006;29:341-2 pubmed..Correction of FAO is related to a drug-induced increase of residual enzyme activity, and this could provide a new treatment strategy for these disorders. ..
- Honda K, Kamisoyama H, Tominaga Y, Yokota S, Hasegawa S. The molecular mechanism underlying the reduction in abdominal fat accumulation by licorice flavonoid oil in high fat diet-induced obese rats. Anim Sci J. 2009;80:562-9 pubmed publisher..Thus, we infer that the natural ingredient LFO is a promising candidate for use as a feed additive to reduce abdominal fat accumulation in domestic animals...
- Beattie S, Goetzman E, Tang Q, Conlon T, Campbell Thompson M, Matern D, et al. Recombinant adeno-associated virus-mediated gene delivery of long chain acyl coenzyme A dehydrogenase (LCAD) into LCAD-deficient mice. J Gene Med. 2008;10:1113-23 pubmed publisher..Mice deficient for long chain acyl CoA dehydrogenase (LCAD) closely resemble the clinical syndrome observed in VLCAD-deficient humans...
- Tucci S, Krogmann A, Herebian D, Spiekerkoetter U. Renal response to short- and long-term exercise in very-long-chain acyl-CoA dehydrogenase-deficient (VLCAD(-/-)) mice. Mol Cell Pediatr. 2014;1:5 pubmed publisher..Our data demonstrate that despite Acadvl ablation, the kidney of VLCAD(-/-) mice fully compensates for impaired fatty acid oxidation by enhanced glycogen utilization and preserves renal energy metabolism and function. ..
- Muroya Y, Ito O. Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats. Clin Exp Nephrol. 2016;20:862-870 pubmed..Clofibrate is protective against renal lipotoxicity in PAN nephrosis. This study indicates that clofibrate has renoprotective effects through maintaining fatty acid metabolism in the kidney of PAN-induced nephrotic rats. ..