Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic phosphoenolpyruvate carboxykinase (EC 4.1.1.32; PEPCK-C) catalyzes the critical regulated step in adipocyte glyceroneogenesis. Numerous studies have shown that hormones and nutrients regulate PEPCK-C at the transcriptional level. We identified two upstream cis-acting DNA elements, gAF1/PCK1 and PCK2, that control adipocyte specific transcription of the PEPCK-C gene (Pck1). Both elements are direct repeat hexanucleotides separated by 1 bp (DR1 elements; variations of the sequence AGGTCAnAGGTCA). PCK2 is located 1 kbp upstream and is the essential element of an adipocyte specific enhancer. It is a peroxisome proliferator activated receptor gamma response element (PPRE) and directs the activation of the PEPCK-C gene during adipogenesis. In addition, it is a thiazolidinedione response element in mature adipocytes. In contrast, gAF1/PCK1, centered 445 bp upstream, is a pleiotropic element that mediates tissue specific glucocorticoid action-repression in adipocytes and induction in hepatocytes. It is a negative response element for PPARgamma, RXRalpha, COUP-TFII, and several unidentified proteins in some cell types, and a positive element for COUP-TFI and HNF4 in other cells type. The purpose of this presentation is to review the discovery and characterization of these two elements in adipocytes and describe how our work has contributed to understanding the mechanisms that control adipocyte glyceroneogenesis.
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PMID:Regulation of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes. 1473 72

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) is the key enzyme in glyceroneogenesis, an important metabolic pathway in adipocytes for reesterification of fatty acids during fasting. Dysregulation of glyceroneogenesis could play a role in the increase in plasma non-esterified fatty acids that accompanies type 2 diabetes. In rodent adipocyte transcription of the PEPCK-C gene is induced by thiazolidinediones (TZDs) through an element, named PCK2, in its promoter. PCK2 binds a peroxisome proliferator activated receptor gamma (PPARgamma), retinoid X receptor alpha (RXRalpha) heterodimer. We demonstrated that in cultured human subcutaneous adipose tissue explants, PEPCK-C specific activity and mRNA were induced by 1 microM of the TZD rosiglitazone, respectively, about twofold in 8 h and fivefold in 5 h. Using gel shift experiments, we show that this effect is likely to involve the human PCK2 (hPCK2) element, which binds a protein complex that contains PPARgamma and RXRalpha. We analyzed hPCK2 (position -1031 to -1015 base pairs) and nearby sequences in the PEPCK-C promoter in 403 subjects with type 2 diabetes and 123 non-diabetic controls. The sequence of hPCK2 was not polymorphic, but we detected two C/T single nucleotide polymorphisms (SNPs), in complete linkage disequilibrium, at positions -1097 and -967 bp. Allele and genotype frequencies were not significantly different in patients and controls. However, our results suggest co-dominant effects of C and T-alleles on fasting plasma glucose and glycosylated hemoglobin A1c levels in obese type 2 diabetic patients.
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PMID:Expression of phosphoenolpyruvate carboxykinase gene in human adipose tissue: induction by rosiglitazone and genetic analyses of the adipocyte-specific region of the promoter in type 2 diabetes. 1473 78