acetyl coa carboxylase

Summary

Summary: A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.

Top Publications

  1. Brusselmans K, de Schrijver E, Verhoeven G, Swinnen J. RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res. 2005;65:6719-25 pubmed
  2. Aoki H, Kimura K, Igarashi K, Takenaka A. Soy protein suppresses gene expression of acetyl-coA carboxylase alpha from promoter PI in rat liver. Biosci Biotechnol Biochem. 2006;70:843-9 pubmed
    ..These data suggest that SPI feeding decreased the hepatic contents of ACC alpha mRNA mainly by regulating PI promoter via a nuclear factor(s) other than SREBP-1. ..
  3. Zang Y, Wang T, Xie W, Wang Fischer Y, Getty L, Han J, et al. Regulation of acetyl CoA carboxylase and carnitine palmitoyl transferase-1 in rat adipocytes. Obes Res. 2005;13:1530-9 pubmed
    b>Acetyl CoA carboxylase (ACC) is a key enzyme in energy balance. It controls the synthesis of malonyl-CoA, an allosteric inhibitor of carnitine palmitoyltransferase-1 (CPT-I). CPT-I is the gatekeeper of free fatty acid (FFA) oxidation...
  4. Chalupska D, Lee H, Faris J, Evrard A, Chalhoub B, Haselkorn R, et al. Acc homoeoloci and the evolution of wheat genomes. Proc Natl Acad Sci U S A. 2008;105:9691-6 pubmed publisher
    ..5 Mya. Such variation might result in a significant overestimate of the time since tetraploid wheat formation, which occurred no more than 0.5 Mya. ..
  5. Denechaud P, Bossard P, Lobaccaro J, Millatt L, Staels B, Girard J, et al. ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver. J Clin Invest. 2008;118:956-64 pubmed publisher
    ..Taken together, our results demonstrate that glucose is required for ChREBP functional activity and that LXRs are not necessary for the induction of glucose-regulated genes in liver. ..
  6. Harada N, Oda Z, Hara Y, Fujinami K, Okawa M, Ohbuchi K, et al. Hepatic de novo lipogenesis is present in liver-specific ACC1-deficient mice. Mol Cell Biol. 2007;27:1881-8 pubmed
    ..Therefore, there does not appear to be strict compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver. ..
  7. Tong L. Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol Life Sci. 2005;62:1784-803 pubmed
    ..The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases. ..
  8. Jørgensen S, Wojtaszewski J, Viollet B, Andreelli F, Birk J, Hellsten Y, et al. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle. FASEB J. 2005;19:1146-8 pubmed
  9. Planavila A, Alegret M, Sanchez R, Rodríguez Calvo R, Laguna J, Vázquez Carrera M. Increased Akt protein expression is associated with decreased ceramide content in skeletal muscle of troglitazone-treated mice. Biochem Pharmacol. 2005;69:1195-204 pubmed
    ..These findings implicate ceramide as an important intermediate in the regulation of Akt after troglitazone treatment. ..

More Information

Publications63

  1. Shen Y, Volrath S, Weatherly S, Elich T, Tong L. A mechanism for the potent inhibition of eukaryotic acetyl-coenzyme A carboxylase by soraphen A, a macrocyclic polyketide natural product. Mol Cell. 2004;16:881-91 pubmed
    ..Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes. ..
  2. Barber M, Price N, Travers M. Structure and regulation of acetyl-CoA carboxylase genes of metazoa. Biochim Biophys Acta. 2005;1733:1-28 pubmed
    ..This review focuses on the structure of ACC genes and the putative individual roles of their gene products in fatty acid metabolism, taking an evolutionary viewpoint provided by data in genome databases. ..
  3. Sha L, Fan X, Yang R, Kang H, Ding C, Zhang L, et al. Phylogenetic relationships between Hystrix and its closely related genera (Triticeae; Poaceae) based on nuclear Acc1, DMC1 and chloroplast trnL-F sequences. Mol Phylogenet Evol. 2010;54:327-35 pubmed publisher
    ..Based on these results, we suggest that Hy. coreana, Hy. duthiei, Hy. duthiei ssp. longearistata, Hy. komarovii and Hy. californica should be included in the genus Leymus, and Hy. patula in the genus Elymus. ..
  4. Fediuc S, Gaidhu M, Ceddia R. Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells. J Lipid Res. 2006;47:412-20 pubmed
    ..Here, we provide novel evidence that the AMPK/ACC pathway may operate as a mechanism to sense and respond to the lipid energy charge of skeletal muscle cells. ..
  5. Chajes V, Cambot M, Moreau K, Lenoir G, Joulin V. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res. 2006;66:5287-94 pubmed
    ..These data confirm the importance of lipogenesis in cancer cell survival and indicate that this pathway represents a key target for antineoplastic therapy that, however, might require specific dietary recommendation for full efficacy. ..
  6. Xiao C, Wood C, Huang W, L Abbé M, Gilani G, Cooke G, et al. Tissue-specific regulation of acetyl-CoA carboxylase gene expression by dietary soya protein isolate in rats. Br J Nutr. 2006;95:1048-54 pubmed
    ..The results indicate that the effect of SPI is tissue-specific and that alteration of ACC gene expression rather than phosphorylation status may play a major role in the regulation of ACC activities by soya proteins. ..
  7. Qiang W, Weiqiang K, Qing Z, Pengju Z, Yi L. Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha. Exp Mol Med. 2007;39:535-43 pubmed
    ..In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance. ..
  8. Oh W, Abu Elheiga L, Kordari P, Gu Z, Shaikenov T, Chirala S, et al. Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice. Proc Natl Acad Sci U S A. 2005;102:1384-9 pubmed
  9. Hawley S, Pan D, Mustard K, Ross L, Bain J, Edelman A, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9-19 pubmed
    ..Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta. ..
  10. Xiang S, Tong L. Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction. Nat Struct Mol Biol. 2008;15:295-302 pubmed publisher
    ..There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli...
  11. Bilder P, Lightle S, Bainbridge G, Ohren J, Finzel B, Sun F, et al. The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme. Biochemistry. 2006;45:1712-22 pubmed
    ..0 and 3.0 A, respectively. Both structures reveal a small, independent zinc-binding domain that lacks a complement in the primary sequence or structure of the eukaryotic homologue. ..
  12. Benson B, Meades G, Grove A, Waldrop G. DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: implications for active site communication. Protein Sci. 2008;17:34-42 pubmed
    ..An important mechanistic implication of these observations is that the dual active sites of ACC are functionally connected. ..
  13. Abu Elheiga L, Matzuk M, Kordari P, Oh W, Shaikenov T, Gu Z, et al. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc Natl Acad Sci U S A. 2005;102:12011-6 pubmed
  14. James E, Cronan J. Expression of two Escherichia coli acetyl-CoA carboxylase subunits is autoregulated. J Biol Chem. 2004;279:2520-7 pubmed
    ..These data support a model in which AccB acts as an autoregulator of accBC operon transcription. ..
  15. Harwood H, Petras S, Shelly L, Zaccaro L, Perry D, Makowski M, et al. Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experimental animals. J Biol Chem. 2003;278:37099-111 pubmed
    ..Taken together, These observations indicate that isozyme-nonselective ACC inhibition has the potential to favorably affect risk factors associated with the metabolic syndrome. ..
  16. Hügler M, Krieger R, Jahn M, Fuchs G. Characterization of acetyl-CoA/propionyl-CoA carboxylase in Metallosphaera sedula. Carboxylating enzyme in the 3-hydroxypropionate cycle for autotrophic carbon fixation. Eur J Biochem. 2003;270:736-44 pubmed
    ..Due to its stability the archaeal carboxylase may prove an ideal subject for further structural studies...
  17. Zhang H, Yang Z, Shen Y, Tong L. Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase. Science. 2003;299:2064-7 pubmed
    ..Mutagenesis and kinetic studies reveal the functional roles of conserved residues here. The herbicides target the active site of CT, providing a lead for inhibitor development against human ACCs. ..
  18. Nikolau B, Ohlrogge J, Wurtele E. Plant biotin-containing carboxylases. Arch Biochem Biophys. 2003;414:211-22 pubmed
    ..This minireview summarizes the recent developments in our understanding of the structure, regulation, and metabolic functions of these proteins in plants. ..
  19. Højlund K, Mustard K, Staehr P, Hardie D, Beck Nielsen H, Richter E, et al. AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes. Am J Physiol Endocrinol Metab. 2004;286:E239-44 pubmed
    ..These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity. ..
  20. Jitrapakdee S, Wallace J. The biotin enzyme family: conserved structural motifs and domain rearrangements. Curr Protein Pept Sci. 2003;4:217-29 pubmed
    ..These structural homologies are so extensive as to be highly suggestive of evolutionary relationships between biotin carboxylases and these other enzymes. ..
  21. Wojtaszewski J, Mourtzakis M, Hillig T, Saltin B, Pilegaard H. Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise. Biochem Biophys Res Commun. 2002;298:309-16 pubmed
  22. Abu Elheiga L, Oh W, Kordari P, Wakil S. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci U S A. 2003;100:10207-12 pubmed
    ..These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases. ..
  23. Weatherly S, Volrath S, Elich T. Expression and characterization of recombinant fungal acetyl-CoA carboxylase and isolation of a soraphen-binding domain. Biochem J. 2004;380:105-10 pubmed
    ..Together, these reagents will be useful for structural studies and assay development. ..
  24. De Prado J, Osuna M, Heredia A, De Prado R. Lolium rigidum, a pool of resistance mechanisms to ACCase inhibitor herbicides. J Agric Food Chem. 2005;53:2185-91 pubmed
    ..Analysis of the leaf cuticle surface by scanning electron microscopy showed a greater epicuticular wax density in the leaf cuticles of biotype R1 than in the other biotypes. ..
  25. Gao J, Zhang Y, Yu C, Tan F, Wang L. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice. Biochem Biophys Res Commun. 2016;476:326-332 pubmed publisher
    ..In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice. ..
  26. Brown R, Wilkinson P, Imran S, Wilkinson M. Resistin differentially modulates neuropeptide gene expression and AMP-activated protein kinase activity in N-1 hypothalamic neurons. Brain Res. 2009;1294:52-60 pubmed publisher
    ..As such, resistin may be part of an autocrine/paracrine loop, which may in turn contribute to some of the reported effects of resistin on energy metabolism. ..
  27. Xu J, Liu X, Gao H, Chen C, Deng Q, Huang Q, et al. Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress. Nutrients. 2015;7:8491-502 pubmed publisher
    ..activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression...
  28. Wang H, Luo J, Chen Z, Cao W, Xu H, Gou D, et al. MicroRNA-24 can control triacylglycerol synthesis in goat mammary epithelial cells by targeting the fatty acid synthase gene. J Dairy Sci. 2015;98:9001-14 pubmed publisher
  29. Fuller K, Summers C, Valentine R. Effect of a single bout of aerobic exercise on high-fat meal-induced inflammation. Metabolism. 2017;71:144-152 pubmed publisher
    ..These findings that acute aerobic exercise improves AMPK and NF-κB signaling in human PBMCs contribute support to the anti-inflammatory roles of exercise. ..
  30. Palanivel R, Veluthakal R, McDonald P, Kowluru A. Further evidence for the regulation of acetyl-CoA carboxylase activity by a glutamate- and magnesium-activated protein phosphatase in the pancreatic beta cell: defective regulation in the diabetic GK rat islet. Endocrine. 2005;26:71-7 pubmed
  31. Kim J, Kang E, Park M, Kim J, Kim S, Jeung E, et al. The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins. Environ Toxicol Pharmacol. 2015;40:284-91 pubmed publisher
    ..The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. ..
  32. Zarzycki J, Brecht V, M ller M, Fuchs G. Identifying the missing steps of the autotrophic 3-hydroxypropionate CO2 fixation cycle in Chloroflexus aurantiacus. Proc Natl Acad Sci U S A. 2009;106:21317-22 pubmed publisher
    ..Elements of the 3-hydroxypropionate cycle may be used for the assimilation of small organic molecules. The 3-hydroxypropionate cycle is compared with the Calvin-Benson-Bassham cycle and other autotrophic pathways...
  33. Liu Y, Zalameda L, Kim K, Wang M, McCarter J. Discovery of acetyl-coenzyme A carboxylase 2 inhibitors: comparison of a fluorescence intensity-based phosphate assay and a fluorescence polarization-based ADP Assay for high-throughput screening. Assay Drug Dev Technol. 2007;5:225-35 pubmed
    ..Acetyl-coenzyme A carboxylase inhibitors were identified by these high-throughput screening methods and were confirmed in a radiometric high performance liquid chromatography assay of malonyl-coenzyme A production. ..
  34. Milanski M, Souza K, Reis S, Feres N, de Souza L, Arantes V, et al. Soybean diet modulates acetyl-coenzyme A carboxylase expression in livers of rats recovering from early-life malnutrition. Nutrition. 2009;25:774-81 pubmed publisher
  35. Yu Q, Abdallah I, Han H, Owen M, Powles S. Distinct non-target site mechanisms endow resistance to glyphosate, ACCase and ALS-inhibiting herbicides in multiple herbicide-resistant Lolium rigidum. Planta. 2009;230:713-23 pubmed publisher
    ..Glyphosate resistance is due to reduced rates of glyphosate translocation, and resistance to ACCase and ALS herbicides is likely due to enhanced herbicide metabolism involving different cytochrome P450 enzymes...
  36. Zhu X, Zhang L, Chen Q, Wan J, Yang G. Interactions of aryloxyphenoxypropionic acids with sensitive and resistant acetyl-coenzyme a carboxylase by homology modeling and molecular dynamic simulations. J Chem Inf Model. 2006;46:1819-26 pubmed
  37. Cai Y, Song Z, Zhang X, Wang X, Jiao H, Lin H. Increased de novo lipogenesis in liver contributes to the augmented fat deposition in dexamethasone exposed broiler chickens (Gallus gallus domesticus). Comp Biochem Physiol C Toxicol Pharmacol. 2009;150:164-9 pubmed publisher
    ..malic enzyme (ME) and fatty acid synthetase (FAS) were significantly increased, while the mRNA levels of acetyl CoA carboxylase (ACC), ME, and FAS were significantly up-regulated, compared with the control...
  38. Robbins J, Heller W, Hanson M. A comparative genomics approach identifies a PPR-DYW protein that is essential for C-to-U editing of the Arabidopsis chloroplast accD transcript. RNA. 2009;15:1142-53 pubmed publisher
    ..The accD gene encodes the beta carboxyltransferase subunit of acetyl coA carboxylase, which catalyzes the first step in fatty acid biosynthesis in chloroplasts...
  39. He B, Mu Y, Chi W. Effects of inefficient transcription termination of rbcL on the expression of accD in plastids of Arabidopsis thaliana. Photosynth Res. 2015;126:323-30 pubmed publisher
    ..Our study demonstrates that the interplay between accD and upstream rbcL regulates the expression of accD and highlights the significance of transcriptional regulation in plastid gene expression in higher plants. ..
  40. Yang S, Li W, Sumien N, Forster M, Simpkins J, Liu R. Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots. Prog Neurobiol. 2017;157:273-291 pubmed publisher
  41. Xu J, Li L, Wang Y, Li Y, Shan M, Sun S, et al. Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice. J Lipid Res. 2018;59:35-47 pubmed publisher
  42. Ohta M, Fujinami A, Kobayashi N, Amano A, Ishigami A, Tokuda H, et al. Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes. Nutr Res. 2015;35:618-25 pubmed publisher
    ..These findings demonstrate that 4HD and XAG can increase GLUT4-dependent glucose uptake through the LKB1/AMPK signaling pathway in 3T3-L1 adipocytes. ..
  43. Wakil S, Abu Elheiga L. Fatty acid metabolism: target for metabolic syndrome. J Lipid Res. 2009;50 Suppl:S138-43 pubmed publisher
    ..In this review we discuss the role of fatty acid metabolism and its key players, ACC1 and ACC2, in animal evolution and physiology, as related to health and disease. ..
  44. Chien R, Yang Y, Lai E, Mau J. Anti-Inflammation and Lipogenic Inhibition of Taiwanofungus salmonea Mycelium and Grifola frondosa Fruiting Body. Int J Med Mushrooms. 2017;19:629-640 pubmed publisher
    ..These results indicate that T. salmonea and G. frondosa are capable of reducing inflammatory responses and ameliorating NASH, indicating their potential as hepatoprotective dietary supplements...
  45. Manley S, Liu W, Welch D. The KISS1 metastasis suppressor appears to reverse the Warburg effect by shifting from glycolysis to mitochondrial beta-oxidation. J Mol Med (Berl). 2017;95:951-963 pubmed publisher
    ..KISS1 alters fatty acid metabolism. • There may be connections between metastasis and metabolism. • PGC1alpha appears to be downstream mediator of KISS1 metastasis suppression. ..
  46. Betteridge S, Bescós R, Martorell M, Pons A, Garnham A, Stathis C, et al. No effect of acute beetroot juice ingestion on oxygen consumption, glucose kinetics, or skeletal muscle metabolism during submaximal exercise in males. J Appl Physiol (1985). 2016;120:391-8 pubmed publisher
    ..in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise...
  47. Streaker E, Beckett D. The biotin regulatory system: kinetic control of a transcriptional switch. Biochemistry. 2006;45:6417-25 pubmed
    ..The data support a switching mechanism in which BirA's function is dictated by its probability of encountering a particular protein partner. ..
  48. Nørgaard J, Sørensen A, Sørensen M, Andersen J, Sejrsen K. Mammary cell turnover and enzyme activity in dairy cows: effects of milking frequency and diet energy density. J Dairy Sci. 2005;88:975-82 pubmed
  49. Akerele O, Cheema S. A low-fat diet enriched in fish oil increased lipogenesis and fetal outcome of C57BL/6 mice. Reproduction. 2017;154:153-165 pubmed publisher
    ..05), which coincides with an increase in the number of fetuses sustained till day 18.5. These novel findings may be important when designing dietary strategies to optimize reproductive capability and pregnancy outcomes. ..
  50. Zhao S, Ma H, Zou S, Chen W, Zhao R. Hepatic lipogenesis in broiler chickens with different fat deposition during embryonic development. J Vet Med A Physiol Pathol Clin Med. 2007;54:1-6 pubmed
    ..The mRNA expression of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME) and apolipoprotein B100 (apoB100) genes were ..
  51. Zou F, Mao X, Wang N, Liu J, Ou Yang J. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin. 2009;30:1607-15 pubmed publisher
    ..APS can alleviate glucose toxicity by increasing liver glycogen synthesis and skeletal muscle glucose translocation in the T2DM rat model, via activation of AMPK. ..
  52. Thomson D, Fick C, Gordon S. AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions. J Appl Physiol (1985). 2008;104:625-32 pubmed publisher
    ..Stimulated and contralateral resting muscles were removed at 0, 20, and 40 min post-STIM, and AMPK, acetyl CoA carboxylase (ACC), Akt, eukaryotic initiation factor 4E-binding protein (4E-BP1), 70-kDa ribosomal protein S6 kinase (..
  53. Zheng Y, Zhang J, Zhang D. Fatsioside A‑induced apoptotic death of HepG2 cells requires activation of AMP‑activated protein kinase. Mol Med Rep. 2015;12:5679-84 pubmed publisher
    ..Together, these results suggested that fatsioside A‑induced apoptotic death requires AMPK activation in HepG2 cells. ..
  54. Damiano F, Testini M, Tocci R, Gnoni G, Siculella L. Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863:388-398 pubmed publisher
    ..A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed. ..