Propionyl-CoA carboxylase

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Propionyl CoA carboxylase, α subunit
Properties of human protein
Mass / length primary structure 703 amino acids (human)
Cofactor Biotin
Identifier
Gene name PCCA
External IDs
Enzyme classification
EC, category 6.4.1.3 ,  ligase
Response type Carboxylation
Substrate Propionyl-CoA + HCO 3 - + ATP
Products D -methylmalonyl-CoA + ADP + P i
Occurrence
Homology family PCCA
Parent taxon Creature

Propionyl CoA carboxylase, β subunit
Properties of human protein
Mass / length primary structure 539 amino acids (human)
Identifier
Gene name PCCB
External IDs
Enzyme classification
EC, category 6.4.1.3 ,  ligase
Response type Carboxylation
Substrate Propionyl-CoA + HCO 3 - + ATP
Products D -methylmalonyl-CoA + ADP + P i
Occurrence
Homology family accD / PCCB
Parent taxon Creature

The propionyl-CoA carboxylase (abbreviated PCCase or PCC ) is an enzyme that the class of ligases counts and in the mitochondria of animals , plants and fungi occurs, but also in bacteria is found. It catalyzes the conversion of propionyl-CoA to D- methylmalonyl-CoA and thus plays an important role in amino acid and fat metabolism . Propionyl-CoA carboxylase needs the vitamin biotin as a cofactor to function . Defects in the subunits can lead to rare hereditary metabolic diseases.

structure

Propionyl-CoA carboxylase is composed of two different proteins , the α and the β subunit, which each occur several times. The human enzyme is a dodecamer in which six α and six β subunits are combined.

The larger α-subunit houses the biotin molecule, which functions as a prosthetic group , as well as the docking site for ATP and the domain at which biotin is carboxylated . In contrast, the smaller β subunit contains the carboxytransferase domain, where the carboxy group is transferred from biotin to propionyl-CoA.

function

Propionyl-CoA carboxylase plays an important role in the breakdown of the amino acids isoleucine , valine , methionine and threonine , odd and branched fatty acids and the side chain of cholesterol , but also in the utilization of the propionic acid formed by some intestinal bacteria through propionic acid fermentation . The resulting propionyl-CoA is converted into D- methylmalonyl-CoA with consumption of ATP , which after two further transformations enters the citric acid cycle as succinyl-CoA ( anaplerotic reaction ).

The course of the enzymatic reaction is very similar to the mechanism that is also known from pyruvate carboxylase , methylcrotonoyl-CoA carboxylase and acetyl-CoA carboxylase : At the first active center, hydrogen carbonate is activated with the consumption of ATP and then biotin is temporarily activated with it carboxylated. The biotin molecule is in turn linked to the protein via a lysine residue and can therefore oscillate back and forth between the two active centers of the enzyme like on a long arm. At the second active center, biotin then releases the carboxy group again to the respective substrate, in this case to propionyl-CoA.

genetics

The gene for the α-subunit (PCCA) encodes in humans on chromosome 13 in the region q32, whereas the gene for the β-subunit (PCCB) is found on chromosome 3 in the region q21-q22.

Several mutations are known from both subunits , which lead to the rare, autosomal recessive inherited metabolic disease propionyl-CoA carboxylase deficiency . A comparatively frequent occurrence is only known among the Inuit in Greenland , as around 5% of all people here have a defective PCCB gene. It is assumed that this is a so-called founder mutation .

Individual evidence

  1. ↑ a b BRENDA enzyme database , entry EC 6.4.1.3 
  2. ↑ Protein database UniProt P05165
  3. ↑ Protein database UniProt P05166
  4. ↑ a b J. M. Berg, JL Tymoczko, L. Stryer: Biochemie. 6th edition. Spectrum Academic Publishing House, Elsevier GmbH, Munich 2007; Pp. 697f, 741ff; ISBN 978-3-8274-1800-5
  5. ^ D. Doenecke, J. Koolman, G. Fuchs, W. Gerok: Karlsons Biochemie und Pathobiochemie. 15th edition. Georg Thieme Verlag, Stuttgart 2005; Pp. 281, 328f, 468, 655 ISBN 978-3-13-357815-8
  6. ↑ HUGO gene database , entry PCCA
  7. ^ HUGO gene database, entry PCCB
  8. ↑ PCCA.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ PCCB.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ K. Ravn et al .: High incidence of propionic acidemia in greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta subunit of propionyl CoA carboxylase. In: Am. J. Hum. Genet. 67 (1); July 2000: pp. 203-6. PMID 10820128 doi : 10.1086 / 302971 (full text)

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Degradation of Propionyl-CoA  - Learning and Teaching Materials