Pyruvate carboxylase

Pyruvate carboxylase
Existing structural data : 3bg3 , 3bg9
Properties of human protein
Mass / length primary structure	1158 amino acids
Secondary to quaternary structure	Homotetramer
Cofactor	Biotin, manganese
Identifier
Gene name	Pc
External IDs	OMIM :  608786 UniProt :  P11498
Enzyme classification
EC, category	6.4.1.1 ,  ligase
Substrate	ATP + pyruvate + HCO 3 -
Products	ADP + phosphate + oxaloacetate
Occurrence
Homology family	Pyruvate carboxylase
Parent taxon	Creature
Exceptions	plants
Orthologue
	human	House mouse
Entrez	5091	18563
Ensemble	ENSG00000173599	ENSMUSG00000024892
UniProt	P11498
Refseq (mRNA)	NM_000920	NM_001162946
Refseq (protein)	NP_000911	NP_001156418
Gene locus	Chr 11: 66.85 - 66.96 Mb	Chr 19: 4.51 - 4.62 Mb
PubMed search	5091	18563

Pyruvate carboxylase (PC) is an enzyme . It catalyzes the addition of carbon dioxide to pyruvate in all living things (except plants ) . This reaction represents the first step in gluconeogenesis and also serves as an anaplerotic reaction for the citric acid cycle . The enzyme is localized in the mitochondria and is allosterically regulated via the concentration of acetyl-CoA . The enzyme function is critically dependent on this regulation, so that in the absence of acetyl-CoA practically no activity can be determined. Mutations on PC - gene in humans can cause rare PC deficiency.

structure

In the mainly active form, the enzyme is present as a (hetero-) tetramer, which is in equilibrium with the dimers and monomers. However, the tetrameric state is not necessary for the basic enzyme function, so that the di- and monomers also have an activity. The molecular weight of a single monomer is 130 kDa.

The most functionally interesting sections of the protein are the N- and C-terminal end pieces. The first 300 to 350 N-terminal amino acids form an ATP binding domain ( ATP-grasp domain ) and the outermost 80 C-terminal amino acids form the biotin binding domain, in which the biotin is covalently linked to the amino group of a lysine via an amide bond . ${\displaystyle \epsilon }$

Reaction mechanism

The exact reaction mechanism of pyruvate carboxylase comprises three steps:

1. Activation of CO ₂ (which is present in aqueous solution as a hydrogen carbonate anion HCO ₃ ^- ) to carboxyphosphate:

   ${\displaystyle \mathrm {HCO_{3}^{-}+\ ATP\longrightarrow HOCO_{2}{\mathord {-}}PO_{3}^{2-}+ADP} }$

2. Attachment of the carboxyphosphate to the biotin (N1 atom):

   ${\displaystyle \mathrm {Enzym{\mathord {-}}Biotin+HOCO_{2}{\mathord {-}}PO_{3}^{2-}+{\text{2 }}H_{2}O\longrightarrow Enzym{\mathord {-}}Biotin{\mathord {-}}COO^{-}+P_{i}+{\text{2 }}H_{3}O^{+}} }$

3. Transfer of the activated carboxy group to the pyruvate:

   ${\displaystyle \mathrm {Enzym{\mathord {-}}Biotin{\mathord {-}}COO^{-}+Pyruvat\longrightarrow Enzym{\mathord {-}}Biotin+Oxalacetat} }$

By using biotin as a coenzyme, the pyruvate carboxylase, like any other biotin-dependent enzyme, is also susceptible to being inhibited by avidin , since it irreversibly binds biotin as an avidin (biotin) ₄ complex.

A malfunction or a lack of the enzyme leads to a pyruvate carboxylase deficiency .

literature

• Stryer et al .: Biochemistry . 5th edition Spektrum Akademischer Verlag, 2003
• Fallert-Müller et al .: Lexicon of Biochemistry , Spektrum Akademischer Verlag, 2000

Individual evidence

1. ↑ UniProt P11498