PEPCK1 (PCK1) Antibody – Goat Polyclonal

Function: Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.

Catalytic activity: GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO2.

Cofactor: Binds 1 manganese ion per subunit. Ref.12

Enzyme regulation: Enzyme activity is enhanced by acetylation. Ref.10

Pathway: Carbohydrate biosynthesis; gluconeogenesis.

Subunit structure: Monomer.

Subcellular location: Cytoplasm.

Tissue specificity: Major sites of expression are liver, kidney and adipocytes.

Induction: Regulated by cAMP and insulin. Ref.9 Ref.10

Post-translational modification: Lysine acetylation by p300/EP300 is increased on high glucose conditions and promotes ubiquitination by UBR5, acetylation is enhanced in the presence of BAG6. Deacetylated by SIRT2.Ubiquitination by UBR5 leads to proteasomal degradation.

Involvement in disease: Cytosolic phosphoenolpyruvate carboxykinase deficiency (C-PEPCKD) [MIM:261680]: Metabolic disorder resulting from impaired gluconeogenesis. It is a rare disease with less than 10 cases reported in the literature. Clinical characteristics include hypotonia, hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia. Autopsy reveals fatty infiltration of both the liver and kidneys. The disorder is transmitted as an autosomal recessive trait.Note: The disease is caused by mutations affecting the gene represented in this entry.

Miscellaneous: In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.

Sequence similarities: Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.