Oxaloacetate decarboxylase

Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase Na+ pump from Vibrio cholerae[1]

Oxaloacetate decarboxylase catalyzes the break down of oxaloacetate into pyruvate and carbon dioxide

oxaloacetate decarboxylase

Identifiers
EC no.| 4.1.1.3
CAS no.| 9024-98-0
Databases
IntEnz| IntEnz view
BRENDA| BRENDA entry
ExPASy| NiceZyme view
KEGG| KEGG entry
MetaCyc| metabolic pathway
PRIAM| profile
PDB structures| RCSB PDB PDBe PDBsum
Gene Ontology| AmiGO  / QuickGO
| Search

PMC| articles
PubMed| articles
NCBI| proteins
Na+-transporting oxaloacetate decarboxylase beta subunit

Identifiers
Symbol| OAD_beta
Pfam| PF03977
Pfam clan| CL0064
InterPro| IPR005661
TCDB| 3.B.1
| Available protein structures:

Pfam | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary
Oxaloacetate decarboxylase, gamma chain

Identifiers
Symbol| OAD_gamma
Pfam| PF04277
InterPro| IPR005899
TCDB| 3.B.1
| Available protein structures:

Pfam | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary

Oxaloacetate decarboxylase is a carboxy-lyase involved in the conversion of oxaloacetate into pyruvate.

It is categorized under EC 4.1.1.3.

Oxaloacetate decarboxylase activity in a given organism may be due to activity of malic enzyme, pyruvate kinase, malate dehydrogenase, pyruvate carboxylase and PEP carboxykinase or the activity of "real" oxaloacetate decarboxylases. The latter enzymes catalyze the irreversible decarboxylation of oxaloacetate and can be classified into (i) the divalent cation-dependent oxaloacetate decarboxylases and (ii) the membrane-bound sodium-dependent and biotin-containing oxaloacetate decarboxylases from enterobacteria.[2][3]

## Contents

* 1 Kinetic Properties
* 2 Cytoplasmic Enzymes
* 3 Membrane-Bound Enzymes
* 4 See also
* 5 References
* 6 Further reading
* 7 External links

## Kinetic Properties[edit]

An oxaloacetate decarboxylase from the family of divalent cation dependent decarboxylases was isolated from Corynebacterium glutamicum in 1995 by Jetten et al. This enzyme selectively catalyzed the decarboxylation of oxaloacetate to pyruvate and CO2 with a Km of 2.1mM, Vmax of 158 umol, and kcat of 311 s^-1.[3] Mn2+ was required for enzymatic activity with a Km of 1.2mM for Mn2+.

A oxaloacetate decarboxylase found in mitochondria and soluble cytoplasm was isolated and purified from rat liver cells in 1974 by Wojtcak et al. The enzyme was not activated by divalent cations nor inhibited by chelating agents. The determined Km value was 0.55mM and the pH optimum for the enzyme between 6.5 and 7.5.[4]

## Cytoplasmic Enzymes[edit]

Found in different microorganisms such as Pseudomonas, Acetobacter, C. glutamicum, Veillonella parvula, and A. vinelandii, cytoplasmic oxaloacetate decarboxylases are dependent on the presence of divalent cations such as Mn2+
, Co2+
, Mg2+
, Ni2+
, or Ca2+
. These enzymes are inhibited by acetyl-CoA and ADP.[2]

## Membrane-Bound Enzymes[edit]

Membrane bound oxaloacetate decarboxylase was the first enzyme of the Na+ transport decarboxylase family demonstrated to act as primary Na+ pump.[5] This enzyme family includes methylmalonyl-CoA decarboxylase, malonate decarboxylase, and glutanoyl-CoA decarboxylase, all of which are found exclusively in anaerobic bacteria.[6]

Decarboxylating the beta-keto acid of oxaloacetate affords the necessary free energy to pump sodium ions across the lipid bilayer. The resulting sodium gradient drives the synthesis of ATP, solute transport, and motility.[7] The overall reaction catalyzed by the pump is the exchange of two intracellular Na+ ions for one extra cellular H+ ion; the reaction is initiated by the enzyme-catalyzed decarboxylation of oxaloacetate in the carboxyltransferase domain of the alpha subunit, yielding pyruvate and carboxybiotin.[8] The oxaloacetate decaboxylase pump is also reversible: at high concentrations of extracellular Na+, the pump will couple downhill movement of Na+ into the cytosol with the carboxylation of pyruvate to form oxaloacetate.[9]

Members of this family of enzymes are typically trimers, composed of alpha, beta and gamma subunits.[10][11] The beta and gamma subunits are integral membrane proteins.[11][12] The ~45kDa beta subunit has nine transmembrane segments which serve to couple the decarboxylation of the carboxybiotin to the translocation of Na+ from the cytoplasm to the periplasm.[7] The small ~9kDa gamma subunit is an integral membrane protein with a single helix at the N-terminus, followed by a hydrophilic C-terminal domain which interacts with the alpha subunit. The gamma subunit is essential for the overall stability of the complex, and likely serves as an anchor to hold the alpha and beta subunits in place.[13][14] Furthermore, the gamma subunit significantly accelerates the rate of oxaloacetate decarboxylation in the alpha subunit, and this correlates with the coordination of a Zn2+ metal ion by several residues at the hydrophilic C-terminus.[8]

The alpha subunit, which is ~65kDa, is a biotinylated peripheral membrane protein on the cytosolic side of the membrane.[8] Within the alpha subunit is the carboxyl transferase (CT) domain, oxaloacetate decarboxylase gamma association domain, and biotin carboxyl carrier domain. The crystal structure of the CT domain forms a TIM barrel fold in a dimer formation that coordinates with a Zn2+ ion in a catalytic site.[13] The enzyme is completely inactivated by specific mutagenesis of Asp17, His207, and His209, which serve as ligands for the Zn2+ metal ion, or by Lys178 near the active site, suggesting that Zn2+ as well as Lys178 are essential for catalysis.[6]

## See also[edit]

* Pyruvate carboxylase

## References[edit]

1. ^ Studer, Remo; Dahinden, Pius; Wang, Wei-Wu; Auchli, Yolanda; Li, Xiao-Dan; Dimroth, Peter (2007-03-23). "Crystal Structure of the Carboxyltransferase Domain of the Oxaloacetate Decarboxylase Na+ Pump from Vibrio cholerae". Journal of Molecular Biology. 367 (2): 547–557. doi:10.1016/j.jmb.2006.12.035. ISSN 0022-2836. PMID 17270211.
2. ^ a b Sauer U, Eikmanns BJ (September 2005). "The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria". FEMS Microbiology Reviews. 29 (4): 765–94. doi:10.1016/j.femsre.2004.11.002. PMID 16102602.
3. ^ a b Jetten MS, Sinskey AJ (1995). "Purification and properties of oxaloacetate decarboxylase from Corynebacterium glutamicum". Antonie van Leeuwenhoek. 67 (2): 221–7. doi:10.1007/bf00871217. PMID 7771770. S2CID 20685117.
4. ^ Wojtczak AB, Walajtys E (May 1974). "Mitochondrial oxaloacetate decarboxylase from rat liver". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 347 (2): 168–82. doi:10.1016/0005-2728(74)90042-5. PMID 4407365.
5. ^ Dimroth P (January 1982). "The generation of an electrochemical gradient of sodium ions upon decarboxylation of oxaloacetate by the membrane-bound and Na+-activated oxaloacetate decarboxylase from Klebsiella aerogenes". European Journal of Biochemistry. 121 (2): 443–9. doi:10.1111/j.1432-1033.1982.tb05807.x. PMID 7037396.
6. ^ a b PDB: 2NX9​; Studer R, Dahinden P, Wang WW, Auchli Y, Li XD, Dimroth P (March 2007). "Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase Na+ pump from Vibrio cholerae". Journal of Molecular Biology. 367 (2): 547–57. doi:10.1016/j.jmb.2006.12.035. PMID 17270211.
7. ^ a b Dimroth P, Jockel P, Schmid M (May 2001). "Coupling mechanism of the oxaloacetate decarboxylase Na(+) pump". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1505 (1): 1–14. doi:10.1016/S0005-2728(00)00272-3. PMID 11248184.
8. ^ a b c Lietzan AD, St Maurice M (February 2014). "Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity". Archives of Biochemistry and Biophysics. Cofactor Assisted Enzymatic Catalysis. 544: 75–86. doi:10.1016/j.abb.2013.10.014. PMID 24184447.
9. ^ Dimroth P, Hilpert W (1984-10-01). "Carboxylation of pyruvate and acetyl coenzyme A by reversal of the sodium pumps oxaloacetate decarboxylase and methylmalonyl-CoA decarboxylase". Biochemistry. 23 (22): 5360–5366. doi:10.1021/bi00317a039.
10. ^ Bott M, Pfister K, Burda P, Kalbermatter O, Woehlke G, Dimroth P (December 1997). "Methylmalonyl-CoA decarboxylase from Propionigenium modestum--cloning and sequencing of the structural genes and purification of the enzyme complex". European Journal of Biochemistry. 250 (2): 590–9. doi:10.1111/j.1432-1033.1997.0590a.x. PMID 9428714.
11. ^ a b Laussermair E, Schwarz E, Oesterhelt D, Reinke H, Beyreuther K, Dimroth P (September 1989). "The sodium ion translocating oxaloacetate decarboxylase of Klebsiella pneumoniae. Sequence of the integral membrane-bound subunits beta and gamma". The Journal of Biological Chemistry. 264 (25): 14710–5. PMID 2549031.
12. ^ Schmid M, Wild MR, Dahinden P, Dimroth P (January 2002). "Subunit gamma of the oxaloacetate decarboxylase Na(+) pump: interaction with other subunits/domains of the complex and binding site for the Zn(2+) metal ion". Biochemistry. 41 (4): 1285–92. doi:10.1021/bi015764l. PMID 11802728.
13. ^ a b Inoue M, Li X (November 2015). "Highly active and stable oxaloacetate decarboxylase Na⁺ pump complex for structural analysis". Protein Expression and Purification. 115: 34–8. doi:10.1016/j.pep.2015.05.008. PMID 25986323.
14. ^ Di Berardino M, Dimroth P (August 1995). "Synthesis of the oxaloacetate decarboxylase Na+ pump and its individual subunits in Escherichia coli and analysis of their function". European Journal of Biochemistry. 231 (3): 790–801. doi:10.1111/j.1432-1033.1995.tb20763.x. PMID 7649179.

## Further reading[edit]

* Dahinden P, Auchli Y, Granjon T, Taralczak M, Wild M, Dimroth P (February 2005). "Oxaloacetate decarboxylase of Vibrio cholerae: purification, characterization, and expression of the genes in Escherichia coli" (PDF). Archives of Microbiology. 183 (2): 121–9. doi:10.1007/s00203-004-0754-5. hdl:20.500.11850/33874. PMID 15647905. S2CID 30038827.

## External links[edit]

* oxaloacetate+decarboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR005661

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Carbon–carbon lyases (EC 4.1)

4.1.1: Carboxy-lyases|

* Acetoacetate decarboxylase
* Adenosylmethionine decarboxylase
* Arginine decarboxylase
* Aromatic L-amino acid decarboxylase
* Glutamate decarboxylase
* Histidine decarboxylase
* Lysine decarboxylase
* Malonyl-CoA decarboxylase
* Ornithine decarboxylase
* Oxaloacetate decarboxylase
* Phosphoenolpyruvate carboxykinase
* Phosphoenolpyruvate carboxylase
* Phosphoribosylaminoimidazole carboxylase
* Pyrophosphomevalonate decarboxylase
* Pyruvate decarboxylase
* RuBisCO
* Uridine monophosphate synthetase/Orotidine 5'-phosphate decarboxylase
* Uroporphyrinogen III decarboxylase

4.1.2: Aldehyde-lyases|

* Fructose-bisphosphate aldolase
* Aldolase A
* Aldolase B
* Aldolase C
* 2-hydroxyphytanoyl-CoA lyase
* Threonine aldolase

4.1.3: Oxo-acid-lyases|

* Isocitrate lyase
* 3-hydroxy-3-methylglutaryl-CoA lyase

4.1.99: Other|

* Tryptophanase
* Photolyase
* CPD lyase
* Spore photoproduct lyase

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Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Diffusion-limited enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
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* EC5 Isomerases (list)
* EC6 Ligases (list)
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