Pck2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox gene
| symbol = PCK2
| name = Phosphoenolpyruvate Carboxykinase 2
| chromosome = 14
| locus = 14q11.2
| geneID = 5106
| omim = 261510
| ensembl = ENSG00000100889
| uniprot = Q16822
| uniprot_name = PCK2
| diseases = Mitochondrial Disorders, Alzheimer's Disease, Hypoglycemia
| diseases_ref = Stauffer et al., 2017, Mol Cell
}}
Phosphoenolpyruvate carboxylase 2 (PCK2) is a mitochondrial enzyme that catalyzes the reversible carboxylation of oxaloacetate (OAA) to phosphoenolpyruvate (PEP) in gluconeogenesis, using GTP as a phosphate donor. The PCK2 gene is located on chromosome 14q12 and encodes a protein of 640 amino acids that localizes to the mitochondrial matrix. Unlike PCK1 (cytosolic), PCK2 is primarily expressed in tissues with high gluconeogenic activity including liver, kidney, and brain. In neurons, PCK2 supports glucose synthesis from lactate and amino acids, contributing to brain energy homeostasis during fasting or hypoglycemia. PCK2 is implicated in mitochondrial disorders, Alzheimer's disease, and metabolic stress response. The enzyme is regulated by acetyl-CoA (activator) and insulin (inhibitor), linking gluconeogenesis to cellular energy status.
Phosphoenolpyruvate carboxykinase 2 (PCK2) is a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate (PEP), a rate-limiting step in gluconeogenesis and anaplerosis. PCK2 is the mitochondrial isoform, distinct from the cytosolic PCK1.
PCK2 catalyzes: Oxaloacetate + GTP → Phosphoenolpyruvate + GDP + CO2. This reaction is essential for:
PCK2 replenishes TCA cycle intermediates:
PCK2 is located in the mitochondrial matrix and:
PCK2 mutations can cause mitochondrial encephalomyopathy with:
PCK2 expression is altered in AD:
PCK2 deficiency causes severe hypoglycemia due to:
PCK2 is expressed in:
In the brain, PCK2 is expressed in:
The study of Pck2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
İlhan N et al.. "The CSF Levels of Mitochondrial Phosphoenolpyruvate Carboxykinase 2 as a Novel Biomarker in Alzheimer's Disease." Molecular neurobiology (2025) DOI:10.1007/s12035-025-05461-9
Sadeesh EM et al.. "Tissue-Specific Diversity of Nuclear-Encoded Mitochondrial Genes Related to Lipid and Carbohydrate Metabolism in Buffalo." Molecular biotechnology (2026) DOI:10.1007/s12033-025-01386-9
Kanabus M et al.. "The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome." Journal of inherited metabolic disease (2016) DOI:10.1007/s10545-016-9930-4