This enzyme is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. A mitochondrial isozyme of the encoded protein also has been characterized.[1]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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↑Pilz AJ, Willer E, Povey S, Abbott CM (October 1992). "The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2". Ann. Hum. Genet. 56 (Pt 4): 289–93. doi:10.1111/j.1469-1809.1992.tb01155.x. PMID1492743.
Pilz AJ, Willer E, Povey S, Abbott CM (1993). "The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2". Ann. Hum. Genet. 56 (Pt 4): 289–93. doi:10.1111/j.1469-1809.1992.tb01155.x. PMID1492743.
Giralt M, Park EA, Gurney AL, et al. (1991). "Identification of a thyroid hormone response element in the phosphoenolpyruvate carboxykinase (GTP) gene. Evidence for synergistic interaction between thyroid hormone and cAMP cis-regulatory elements". J. Biol. Chem. 266 (32): 21991–6. PMID1657985.
Beale EG, Chrapkiewicz NB, Scoble HA, et al. (1985). "Rat hepatic cytosolic phosphoenolpyruvate carboxykinase (GTP). Structures of the protein, messenger RNA, and gene". J. Biol. Chem. 260 (19): 10748–60. PMID2993287.
Ting CN, Burgess DL, Chamberlain JS, et al. (1993). "Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20". Genomics. 16 (3): 698–706. doi:10.1006/geno.1993.1250. PMID8325643.
Yu H, Thun R, Chandrasekharappa S, et al. (1993). "Human PCK1 encoding phosphoenolpyruvate carboxykinase is located on chromosome 20q13.2". Genomics. 15 (1): 219–21. doi:10.1006/geno.1993.1040. PMID8432541.
Stoffel M, Xiang KS, Espinosa R, et al. (1993). "cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young". Hum. Mol. Genet. 2 (1): 1–4. doi:10.1093/hmg/2.1.1. PMID8490617.
O'Brien RM, Printz RL, Halmi N, et al. (1996). "Structural and functional analysis of the human phosphoenolpyruvate carboxykinase gene promoter". Biochim. Biophys. Acta. 1264 (3): 284–8. doi:10.1016/0167-4781(95)00194-8. PMID8547315.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID11780052.
Dunten P, Belunis C, Crowther R, et al. (2002). "Crystal structure of human cytosolic phosphoenolpyruvate carboxykinase reveals a new GTP-binding site". J. Mol. Biol. 316 (2): 257–64. doi:10.1006/jmbi.2001.5364. PMID11851336.
Jurado LA, Song S, Roesler WJ, Park EA (2002). "Conserved amino acids within CCAAT enhancer-binding proteins (C/EBP(alpha) and beta) regulate phosphoenolpyruvate carboxykinase (PEPCK) gene expression". J. Biol. Chem. 277 (31): 27606–12. doi:10.1074/jbc.M201429200. PMID11997389.
Wilson HL, McFie PJ, Roesler WJ (2003). "Different transcription factor binding arrays modulate the cAMP responsivity of the phosphoenolpyruvate carboxykinase gene promoter". J. Biol. Chem. 277 (46): 43895–902. doi:10.1074/jbc.M203169200. PMID12237288.
Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E (2003). "Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP". J. Biol. Chem. 277 (51): 49761–6. doi:10.1074/jbc.M205641200. PMID12324453.
Chakravarty K, Wu SY, Chiang CM, et al. (2004). "SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver". J. Biol. Chem. 279 (15): 15385–95. doi:10.1074/jbc.M309905200. PMID14744869.
Cao H, van der Veer E, Ban MR, et al. (2004). "Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus". J. Clin. Endocrinol. Metab. 89 (2): 898–903. doi:10.1210/jc.2003-031361. PMID14764811.