ACADL

Summary

Gene Symbol: ACADL
Description: acyl-CoA dehydrogenase long chain
Alias: ACAD4, LCAD, long-chain specific acyl-CoA dehydrogenase, mitochondrial, acyl-Coenzyme A dehydrogenase, long chain
Species: human
Products:     ACADL

Top Publications

  1. Illig T, Gieger C, Zhai G, Römisch Margl W, Wang Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42:137-41 pubmed publisher
    ..For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers ..
  2. Tucci S, Mingirulli N, Wehbe Z, Dumit V, Kirschner J, Spiekerkoetter U. Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice. FEBS Lett. 2017;: pubmed publisher
    ..Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. ..
  3. Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper J. Obesity and aging diminish sirtuin 1 (SIRT1)-mediated deacetylation of SIRT3, leading to hyperacetylation and decreased activity and stability of SIRT3. J Biol Chem. 2017;292:17312-17323 pubmed publisher
    ..Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach for obesity- and aging-related diseases associated with mitochondrial dysfunction. ..
  4. Jiang P, Zhang X, Huang Y, Cheng N, Ma Y. Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats. Molecules. 2017;22: pubmed publisher
    ..was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-α, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells...
  5. Lou P, Lucchinetti E, Scott K, Huang Y, Gandhi M, Hersberger M, et al. Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats. Physiol Rep. 2017;5: pubmed publisher
    ..Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart. ..
  6. Bharathi S, Zhang Y, Mohsen A, Uppala R, Balasubramani M, Schreiber E, et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem. 2013;288:33837-47 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a key mitochondrial fatty acid oxidation enzyme...
  7. Lea W, Abbas A, Sprecher H, Vockley J, Schulz H. Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids. Biochim Biophys Acta. 2000;1485:121-8 pubmed
    ..and 4-cis-decenoic acid were effectively dehydrogenated by both rat and human long-chain acyl-CoA dehydrogenases (LCAD), whereas they were poor substrates of very long-chain acyl-CoA dehydrogenases (VLCAD)...
  8. Hong M, Karlsson R, Magnusson P, Lewis M, Isaacs W, Zheng L, et al. A genome-wide assessment of variability in human serum metabolism. Hum Mutat. 2013;34:515-24 pubmed publisher
    ..Seven replicating loci were identified (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with associated sequence variants contributing significantly to trait variance for one or more ..
  9. 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 its gene to chromosome 2. Prog Clin Biol Res. 1992;375:161-7 pubmed
  10. Costa C, Verhoeven N, Kneepkens C, Douwes A, Wanders R, de Almeida I, et al. Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease. J Inherit Metab Dis. 1996;19:177-80 pubmed

Detail Information

Publications34

  1. Illig T, Gieger C, Zhai G, Römisch Margl W, Wang Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42:137-41 pubmed publisher
    ..For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers ..
  2. Tucci S, Mingirulli N, Wehbe Z, Dumit V, Kirschner J, Spiekerkoetter U. Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice. FEBS Lett. 2017;: pubmed publisher
    ..Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. ..
  3. Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper J. Obesity and aging diminish sirtuin 1 (SIRT1)-mediated deacetylation of SIRT3, leading to hyperacetylation and decreased activity and stability of SIRT3. J Biol Chem. 2017;292:17312-17323 pubmed publisher
    ..Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach for obesity- and aging-related diseases associated with mitochondrial dysfunction. ..
  4. Jiang P, Zhang X, Huang Y, Cheng N, Ma Y. Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats. Molecules. 2017;22: pubmed publisher
    ..was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-α, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells...
  5. Lou P, Lucchinetti E, Scott K, Huang Y, Gandhi M, Hersberger M, et al. Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats. Physiol Rep. 2017;5: pubmed publisher
    ..Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart. ..
  6. Bharathi S, Zhang Y, Mohsen A, Uppala R, Balasubramani M, Schreiber E, et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem. 2013;288:33837-47 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a key mitochondrial fatty acid oxidation enzyme...
  7. Lea W, Abbas A, Sprecher H, Vockley J, Schulz H. Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids. Biochim Biophys Acta. 2000;1485:121-8 pubmed
    ..and 4-cis-decenoic acid were effectively dehydrogenated by both rat and human long-chain acyl-CoA dehydrogenases (LCAD), whereas they were poor substrates of very long-chain acyl-CoA dehydrogenases (VLCAD)...
  8. Hong M, Karlsson R, Magnusson P, Lewis M, Isaacs W, Zheng L, et al. A genome-wide assessment of variability in human serum metabolism. Hum Mutat. 2013;34:515-24 pubmed publisher
    ..Seven replicating loci were identified (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with associated sequence variants contributing significantly to trait variance for one or more ..
  9. 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 its gene to chromosome 2. Prog Clin Biol Res. 1992;375:161-7 pubmed
  10. Costa C, Verhoeven N, Kneepkens C, Douwes A, Wanders R, de Almeida I, et al. Organic acid profiles resembling a beta-oxidation defect in two patients with coeliac disease. J Inherit Metab Dis. 1996;19:177-80 pubmed
  11. 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
    ..The physiological role of long-chain acyl-CoA dehydrogenase (LCAD) has remained obscure, however...
  12. Chen Q, Niu L, Hua C, Geng Y, Cai L, Tao S, et al. Chronic dexamethasone exposure markedly decreased the hepatic triglyceride accumulation in growing goats. Gen Comp Endocrinol. 2017;: pubmed publisher
    ..of sterol regulatory element binding transcription factor 1 (SREBP-1), acyl-CoA dehydrogenase long chain (ACADL) and acyl-CoA synthetase bubblegum family member 1 (ACSBG1) genes in liver was significantly up-regulated by ..
  13. Rueedi R, Ledda M, Nicholls A, Salek R, Marques Vidal P, Morya E, et al. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links. PLoS Genet. 2014;10:e1004132 pubmed publisher
    ..The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. ..
  14. Hale D, Batshaw M, Coates P, Frerman F, Goodman S, Singh I, et al. Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. Pediatr Res. 1985;19:666-71 pubmed
    ..abstract truncated at 250 words) ..
  15. Agarwal N, Iyer D, Gabbi C, Saha P, Patel S, Mo Q, et al. HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRα and PPARα dysregulation: implications for HIV-specific pathogenesis of NAFLD. Sci Rep. 2017;7:13362 pubmed publisher
    ..hepatic fatty acid ß-oxidation was associated with decreased mRNA expression of Pparα and its targets Cpt1, Aox, Lcad, Ehhadh, Hsd10 and Acaa2, and blunted VLDL export with decreased expression of Mttp and its product microsomal ..
  16. Maher A, Mohsen A, Vockley J, Tarnopolsky M. Low expression of long-chain acyl-CoA dehydrogenase in human skeletal muscle. Mol Genet Metab. 2010;100:163-7 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial flavoenzyme thought to be one of the major enzymes responsible for the first step of long-chain fatty acid (LCFA) beta-oxidation...
  17. Ohn J, Hwang J, Moon M, Ahn H, Kim H, Koo Y, et al. Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice. PLoS ONE. 2017;12:e0186021 pubmed publisher
    ..We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD. ..
  18. Zhang Z, Zhou Y, Mendelsohn N, Bauer G, Strauss A. Regulation of the human long chain acyl-CoA dehydrogenase gene by nuclear hormone receptor transcription factors. Biochim Biophys Acta. 1997;1350:53-64 pubmed
    ..Long chain acyl-CoA dehydrogenase (LCAD) catalyzes the first step in the beta-oxidation spiral...
  19. Ryder B, Knoll D, Love D, Shepherd P, Love J, Reed P, et al. The natural history of elevated tetradecenoyl-L-carnitine detected by newborn screening in New Zealand: implications for very long chain acyl-CoA dehydrogenase deficiency screening and treatment. J Inherit Metab Dis. 2016;39:409-414 pubmed publisher
    ..9-2.4 μmol/L, on NBS are at very low risk of clinically significant childhood disease. A minimally interventional approach to managing these patients is indicated, at least in the New Zealand population. ..
  20. Pena L, van Calcar S, Hansen J, Edick M, Walsh Vockley C, Leslie N, et al. Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database. Mol Genet Metab. 2016;118:272-81 pubmed publisher
    ..Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified. ..
  21. Obaid A, Nashabat M, Alfadhel M, Alasmari A, Al Mutairi F, Alswaid A, et al. Clinical, Biochemical, and Molecular Features in 37 Saudi Patients with Very Long Chain Acyl CoA Dehydrogenase Deficiency. JIMD Rep. 2017;: pubmed publisher
    ..The aim of this study was to analyze the clinical, biochemical, and molecular features of VLCAD deficiency in Saudi Arabia, including the treatment and outcome...
  22. Jernberg J, Bowman C, Wolfgang M, Scafidi S. Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain. J Neurochem. 2017;142:407-419 pubmed publisher
    ..Read the Editorial Comment for this article on page 347...
  23. Chowdhury M, Mesalam A, Khan I, Joo M, Lee K, Xu L, et al. Improved Developmental Competence in Embryos Treated with Lycopene during In Vitro Culture. Mol Reprod Dev. 2017;: pubmed publisher
    ..factor 9), BMP15 (Bone morphogenetic protein 15), SOD2 (Superoxide dismutase 2), NDUFA2 (NADH dehydrogenase), ACADL (Acyl-CoA dehydrogenase, long chain), and ACSL3 (Acyl-CoA synthetase 3, long-chain membrane 3) transcription ..
  24. Goetzman E, Alcorn J, Bharathi S, Uppala R, McHugh K, Kosmider B, et al. Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction. J Biol Chem. 2014;289:10668-79 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver...
  25. Evans M, Andresen B, Nation J, Boneh A. VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria. Mol Genet Metab. 2016;118:282-7 pubmed publisher
    ....
  26. Mayatepek E, Flock B. Increased urinary excretion of LTB4 and omega-carboxy-LTB4 in patients with Zellweger syndrome. Clin Chim Acta. 1999;282:151-5 pubmed
    ..Analysis of urinary leukotrienes represents an additional diagnostic tool in peroxisome deficiency disorders. Furthermore, these results clearly underline the essential role of peroxisomes in the oxidation of LTB4 in humans...
  27. 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
    Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepato- and cardiomegaly...
  28. 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
    Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the first reaction of the mitochondrial beta-oxidation of fatty acids. We isolated and sequenced three cDNA clones encoding human LCAD precursor (p)...
  29. Abe T, Fujino T, Fukuyama R, Minoshima S, Shimizu N, Toh H, et al. Human long-chain acyl-CoA synthetase: structure and chromosomal location. J Biochem. 1992;111:123-8 pubmed
    ....
  30. 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. 1992;12:626 pubmed
  31. Merinero B, Alcaide P, Martin Hernandez E, Morais A, Garcia Silva M, Quijada Fraile P, et al. Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers. JIMD Rep. 2017;: pubmed publisher
    ....
  32. Vengalil S, Preethish Kumar V, Polavarapu K, Christopher R, Gayathri N, Natarajan A, et al. Fatty acid oxidation defects presenting as primary myopathy and prominent dropped head syndrome. Neuromuscul Disord. 2017;27:986-996 pubmed publisher
    ..Hitherto, unreported we describe "dropped head syndrome" as a prominent phenomenon in MCAD and VLCAD. The presence of ptosis and bulbar weakness in fatty acid oxidation defects expands the clinical spectrum. ..
  33. Vivod R, Oetermann S, Hiessl S, Gutsche S, Remmers N, Meinert C, et al. Oligo(cis-1,4-isoprene) aldehyde-oxidizing dehydrogenases of the rubber-degrading bacterium Gordonia polyisoprenivorans VH2. Appl Microbiol Biotechnol. 2017;101:7945-7960 pubmed publisher
    ....
  34. Treem W, Stanley C, Hale D, Leopold H, Hyams J. Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency. Pediatrics. 1991;87:328-33 pubmed
    ..This report stresses the enlarging spectrum of the clinical presentation and natural history of this defect in fatty acid oxidation. ..