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MetaCyc Pathway: biotin-carboxyl carrier protein assembly

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: BCCP assembly

Superclasses: Biosynthesis Fatty Acids and Lipids Biosynthesis

Some taxa known to possess this pathway include ? : Aquifex aeolicus , Arabidopsis thaliana col , Bacillus subtilis , Corynebacterium glutamicum , Escherichia coli K-12 substr. MG1655 , Mycobacterium leprae , Mycobacterium tuberculosis , Myxococcus xanthus , Nicotiana tabacum , Pisum sativum , Propionibacterium freudenreichii , Pseudomonas aeruginosa , Ricinus communis

Expected Taxonomic Range: Bacteria , Viridiplantae

Summary:
General Background

Biotin-dependent carboxylases constitute a group of enzymes with many common features in structure and mechanism [Wood77]. These enzymes have been identified in prokaryotic and eukaryotic organisms. Some members of this family include acetyl-CoA carboxylase, propionyl-CoA carboxylase, pyruvate decarboxylase and the Propionibacterium freudenreichii transcarboxylase [Thornton93]. These enzymes are involved in various metabolic reactions such as lipogenesis, gluconeogenesis, and amino acid metabolism. Another group of bioin-dependent enzymes are the decarboxylases mediating sodium transport [Samols88] (for an example, see biotin-dependent malonate decarboxylase from Malonomonas rubra).

The different biotin-dependent enzymes have different architectures in different organisms. For example, eukaryotic acetyl-CoA carboxylases contain three functional modules in one large polypeptide (biotin carboxylase/biotin-carboxyl-carrier protein/carboxyltransferase), eukaryotic propionyl-CoA-carboxylases and bifunctional acetyl/propionyl-CoA carboxylases of Mycobacteria are composed of a coupled biotin carboxylase/biotin-carboxyl-carrier protein polypeptide and separate carboxyltransferase proteins, while all the subunits of Escherichia coli acetyl-CoA carboxylase exist as single proteins [Toh93, Norman94, Jager96].

About This Pathway

The enzyme acetyl-CoA carboxylase is one of the key enzymes in the biosynthesis of fatty acids (see superpathway of fatty acid biosynthesis initiation (E. coli)). The Escherichia coli K-12 enzyme complex is composed of two catalytic units and one carrier protein, encoded by four different genes. The catalytic units are biotin carboxylase (BC), a homodimer encoded by the accC gene, and acetyl-CoA carboxylase (ACCT), an α2β2 tetramer, encoded by the accA and accD genes. The carrier protein is the biotin carboxyl carrier protein (BCCP), a homodimer encoded by the accB gene.

The BCCP monomer is biotinylated by the enzyme biotin-[acetyl-CoA-carboxylase] ligase. Following dimerization of the biotinylated monomers, biotin carboxylase (BC) catalyzes the addition of CO2 to the carrier protein dimer, forming a carboxylated-biotinylated [BCCP dimer] (carboxy-BCCP). a carboxylated-biotinylated [BCCP dimer] in turn is the substrate for ACCT, which transfers the carboxy group to acetyl-CoA, resulting in the formation of malonyl-CoA and the regeneration of biotin carboxyl carrier protein (dimer). Both biotinylation and carboxylation of the carrier protein require ATP, while the last step, transfer of the carboxy group to acetyl-CoA, does not [Barber05].

The pathway has been summarized by the EC reaction 6.4.1.2 , as follows:

ATP + acetyl-CoA + hydrogen carbonate → malonyl-CoA + ADP + phosphate + H+

Unification Links: AraCyc:PWY0-1264 , EcoCyc:PWY0-1264

Credits:
Created 01-Feb-2006 by Caspi R , SRI International


References

Barber05: Barber MC, Price NT, Travers MT (2005). "Structure and regulation of acetyl-CoA carboxylase genes of metazoa." Biochim Biophys Acta 1733(1);1-28. PMID: 15749055

Jager96: Jager W, Peters-Wendisch PG, Kalinowski J, Puhler A (1996). "A Corynebacterium glutamicum gene encoding a two-domain protein similar to biotin carboxylases and biotin-carboxyl-carrier proteins." Arch Microbiol 166(2);76-82. PMID: 8772169

Norman94: Norman E, De Smet KA, Stoker NG, Ratledge C, Wheeler PR, Dale JW (1994). "Lipid synthesis in mycobacteria: characterization of the biotin carboxyl carrier protein genes from Mycobacterium leprae and M. tuberculosis." J Bacteriol 176(9);2525-31. PMID: 7909542

Samols88: Samols D, Thornton CG, Murtif VL, Kumar GK, Haase FC, Wood HG (1988). "Evolutionary conservation among biotin enzymes." J Biol Chem 263(14);6461-4. PMID: 2896195

Thornton93: Thornton CG, Kumar GK, Haase FC, Phillips NF, Woo SB, Park VM, Magner WJ, Shenoy BC, Wood HG, Samols D (1993). "Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli." J Bacteriol 175(17);5301-8. PMID: 8366018

Toh93: Toh H, Kondo H, Tanabe T (1993). "Molecular evolution of biotin-dependent carboxylases." Eur J Biochem 215(3);687-96. PMID: 8102604

Wood77: Wood, H.G., Barden, R.E. (1977). "Biotin enzymes." Annu. Rev. Biochem. 46: 385-413.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Abbott93: Abbott J, Beckett D (1993). "Cooperative binding of the Escherichia coli repressor of biotin biosynthesis to the biotin operator sequence." Biochemistry 32(37);9649-56. PMID: 8373769

AbdelHamid07: Abdel-Hamid AM, Cronan JE (2007). "Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli." J Bacteriol 189(2);369-76. PMID: 17056747

Alban00: Alban C, Job D, Douce R (2000). "Biotin metabolism in plants." Annu Rev Plant Physiol Plant Mol Biol 51;17-47. PMID: 15012185

Alberts68: Alberts AW, Vagelos PR (1968). "Acetyl CoA carboxylase. I. Requirement for two protein fractions." Proc Natl Acad Sci U S A 59(2);561-8. PMID: 4868901

Alberts69a: Alberts AW, Nervi AM, Vagelos PR (1969). "Acetyl CoA carboxylase, II. Deomonstration of biotin-protein and biotin carboxylase subunits." Proc Natl Acad Sci U S A 63(4);1319-26. PMID: 4901473

Alberts71: Alberts AW, Gordon SG, Vagelos PR (1971). "Acetyl CoA carboxylase: the purified transcarboxylase component." Proc Natl Acad Sci U S A 68(6);1259-63. PMID: 4942182

Allison38: Allison, F. E., Minor, F. W. (1938). "Coenzyme R requirements of rhizobia." Soil Sc.i 46:473-483.

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Barker80: Barker DF, Campbell AM (1980). "Use of bio-lac fusion strains to study regulation of biotin biosynthesis in Escherichia coli." J Bacteriol 143(2);789-800. PMID: 6782078

Barker81: Barker DF, Campbell AM (1981). "Genetic and biochemical characterization of the birA gene and its product: evidence for a direct role of biotin holoenzyme synthetase in repression of the biotin operon in Escherichia coli." J Mol Biol 146(4);469-92. PMID: 6456358

Barker81a: Barker DF, Campbell AM (1981). "The birA gene of Escherichia coli encodes a biotin holoenzyme synthetase." J Mol Biol 146(4);451-67. PMID: 7024555

Beckett07: Beckett D (2007). "Biotin Sensing: Universal Influence of Biotin Status on Transcription." Annu Rev Genet 41:443-64. PMID: 17669049

Beckett98: Beckett D (1998). "Energetic methods to study bifunctional biotin operon repressor." Methods Enzymol 295;424-50. PMID: 9750231

Beckett99: Beckett D, Kovaleva E, Schatz PJ (1999). "A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation." Protein Sci 8(4);921-9. PMID: 10211839

Benson08: Benson BK, Meades G, Grove A, Waldrop GL (2008). "DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: implications for active site communication." Protein Sci 17(1);34-42. PMID: 18156466

Bilder06: Bilder P, Lightle S, Bainbridge G, Ohren J, Finzel B, Sun F, Holley S, Al-Kassim L, Spessard C, Melnick M, Newcomer M, Waldrop GL (2006). "The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme." Biochemistry 45(6);1712-22. PMID: 16460018

Blanchard98a: Blanchard CZ, Waldrop GL (1998). "Overexpression and kinetic characterization of the carboxyltransferase component of acetyl-CoA carboxylase." J Biol Chem 273(30);19140-5. PMID: 9668099

Blanchard99: Blanchard CZ, Chapman-Smith A, Wallace JC, Waldrop GL (1999). "The biotin domain peptide from the biotin carboxyl carrier protein of Escherichia coli acetyl-CoA carboxylase causes a marked increase in the catalytic efficiency of biotin carboxylase and carboxyltransferase relative to free biotin." J Biol Chem 1999;274(45);31767-9. PMID: 10542197

Blanchard99a: Blanchard CZ, Amspacher D, Strongin R, Waldrop GL (1999). "Inhibition of biotin carboxylase by a reaction intermediate analog: implications for the kinetic mechanism." Biochem Biophys Res Commun 1999;266(2);466-71. PMID: 10600526

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, BIOCYC13A.