PC carboxylates PYR to OA

Stable Identifier
Reaction [transition]
Homo sapiens
PC catalyzes the carboxylation of PYR to form OA, ATP + hydrogencarbonate + pyruvate => ADP + H(+) + oxaloacetate + phosphate
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Mitochondrial pyruvate carboxylase (PC) catalyzes the irreversible reaction of pyruvate (PYR), bicarbonate (HCO3-), and ATP to form oxaloacetate (OA), ADP, phosphate, (Pi), and H+. The enzyme is biotinylated and is active as a tetramer. The protein structure and function have been characterized in detail (Jitrapakdee et al., 2008; Jitrapakdee & Wallace, 1999; Lopez-Alonso et al., 2022). The reaction proceeds in two steps, with the biotin modification carboxylated first (Wexler et al., 1998). It is highly sensitive to activation by acetyl-CoA and gets inhibited by 2-oxoglutarate, L-malate, and L-glutamate (Scrutton & White, 1974; Jitrapakdee et al., 2008). Activation of PC by acetyl-CoA produced from lipolysis and leading to excess gluconeogenesis is the central mechanism of metabolic syndrome and diabetes (reviewed in Lao-On et al., 2018). Both normal and defective forms of the human enzyme have been described, with deficiency leading to lactic acidosis and potentially intellectual disability and death (MIM:266150; Carbone & Robinson, 2003; reviewed in Marin-Valencia et al., 2010).
Literature References
PubMed ID Title Journal Year
12437512 Expression and characterization of a human pyruvate carboxylase variant by retroviral gene transfer

Robinson, BH, Carbone, MA

Biochem J 2003
10229653 Structure, function and regulation of pyruvate carboxylase

Jitrapakdee, S, Wallace, JC

Biochem J 1999
4826475 Purification and properties of human liver pyruvate carboxylase

White, MD, Scrutton, MC

Biochem Med 1974
9585002 Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families

Du, Y, Wexler, ID, Kerr, DS, Stephenson, W, Higgins, JJ, Wappner, RS, Kaung, MM, Lusk, MM

Pediatr Res 1998
36261450 CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase

Tong, L, López-Alonso, JP, Choi, PH, Gil-Cartón, D, Lázaro, M, Valle, M, Dodu, A

Nat Commun 2022
20598931 Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis

Pascual, JM, Roe, CR, Marin-Valencia, I

Mol Genet Metab 2010
29362846 Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection

Jitrapakdee, S, Lao-On, U, Attwood, PV

J Mol Med (Berl) 2018
18613815 Structure, mechanism and regulation of pyruvate carboxylase

Jitrapakdee, S, Rayment, I, Wallace, JC, St Maurice, M, Cleland, WW, Attwood, PV

Biochem J 2008
Catalyst Activity

pyruvate carboxylase activity of PC tetramer [mitochondrial matrix]

This event is regulated
Orthologous Events
Cross References
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