Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.1.1.49 (phosphoenolpyruvate carboxykinase)
4,654 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid sequence of the mitochondrial form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-M) from the chicken was deduced from the 3571 nucleotide sequence of three overlapping cDNA clones. The derived protein sequence, which includes 607 amino acids of the mature enzyme and a leader sequence, was aligned with nine tryptic peptides of PEPCK-M and the primary sequence of the cytosolic form of PEPCK from chicken. Secondary structure predictions for the two PEPCK isozymes indicated similar packing elements of conserved, hydrophobic beta strands in the central core of the primary sequence. This core protein, which contained three GTP-binding consensus elements, was 80% identical in the two chicken isozymes, although the overall level of identity was only 63% for amino acids and 60% for nucleotides. The untranslated regions of the two cDNAs were dissimilar, although both mRNAs have potential for significant secondary structure. The PEPCK-M mRNA contained several G-C-rich regions which demonstrated free energies of formation in dyad symmetry programs up to -70 kcal/mol. The 1.6-kilobase (kb) 3'-untranslated region contained several repeat elements including one of 11 base pairs, which was present 30 times; but, a signal sequence for polyadenylation was not present. Each of the three PEPCK-M cDNA clones recognized two mRNAs of 4.2 and 3.4 kb in the livers and kidneys of starved or normally fed chickens. However, the level of these two related PEPCK-M mRNAs changed in response to cAMP treatment, with the larger mRNA predominant at 20 and 160 min and the 3.4-kb mRNA present at intermediate times. In contrast, the level of the 2.8-kb PEPCK-C mRNA increased dramatically upon addition of the cyclic nucleotide, particularly in the liver where it was not detected without cAMP induction. Thus, PEPCK-M and PEPCK-C, clearly represented the products of two distinct genes, which were distinguished by altered protein sequences and non-cross-hybridizing, differentially regulated mRNAs.
...
PMID:Mitochondrial phosphoenolpyruvate carboxykinase from the chicken. Comparison of the cDNA and protein sequences with the cytosolic isozyme. 211 Jan 63

Gluconeogenesis in the chicken has unique features due in part to the presence of two isozymes of PEPCK, a cytosolic form, PEPCK-C, and a mitochondrial form, PEPCK-M, which have novel patterns of expression. Here we show that, in contrast to mammals, in which PEPCK-C is not present in liver until after birth, avian PEPCK-C is expressed throughout embryonic life with mRNA levels gradually decreasing as development proceeds and becoming negligible at time of hatching. In addition two distinct mRNAs for PEPCK-M are expressed during development with specific patterns that vary among individual birds. These differences are likely to be genetic, as hormonal treatment of a chicken hepatoma cell line indicates that whereas the mRNA levels for PEPCK-C are hormonally regulated, the expression of PEPCK-M mRNA is unresponsive.
...
PMID:Expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase in avian liver during development. 839 1

Phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is a key enzyme in the synthesis of glucose in the liver and kidney and of glyceride-glycerol in white adipose tissue and the small intestine. The gene for the cytosolic form of PEPCK (PEPCK-C) is acutely regulated by a variety of dietary and hormonal signals, which result in alteration of synthesis of the enzyme. Major factors that increase PEPCK-C gene expression include cyclic AMP, glucocorticoids, and thyroid hormone, whereas insulin inhibits this process. PEPCK-C is absent in fetal liver but appears at birth, concomitant with the capacity for gluconeogenesis. Regulatory elements that control transcription of the PEPCK-C gene in liver, kidney, and adipose tissue have been delineated, and many of the transcription factors that bind to these elements have been identified. Transgenic mice have been especially useful in elucidating the physiological roles of specific sequence elements in the PEPCK-C gene promoter and in demonstrating the key role played at these sites by the isoforms of CAAT/enhancer binding protein in patterning of PEPCK-C gene expression during the perinatal period. The PEPCK-C gene provides a model for the metabolic control of gene transcription.
...
PMID:Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. 924 18

Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor gamma (PPAR gamma) called the peroxisome proliferator-activated receptor element (PPARE), in the 5' flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE(-/-) mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE(-/-) mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.
...
PMID:A mutation in the peroxisome proliferator-activated receptor gamma-binding site in the gene for the cytosolic form of phosphoenolpyruvate carboxykinase reduces adipose tissue size and fat content in mice. 1179 50

The cytosolic (C) and mitochondrial (M) forms of phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) are encoded by two different nuclear genes in mouse, human, and chicken. Our objective was to clone the two forms of PEPCK for bovine and determine their expression during the immediate periparturient interval in dairy cows. Bovine PEPCK-C cDNA contains 2,592 nucleotides and contains 84% similarity to the coding sequence of human PEPCK-C cDNA. A 449-nt partial clone of the 3' end of PEPCK-M is 76% similar to the corresponding sequence of human PEPCK-M. The coding sequence of bovine PEPCK-C and coding sequence of the partial PEPCK-M clone were 58% similar but the similarities in the 3'-untranslated regions were negligible. Northern blot analysis revealed single transcripts of 2.85 and 2.35 kb for PEPCK-C and PEPCK-M, respectively. The transition to lactation did not alter PEPCK-M transcript expression, but expression of PEPCK-C mRNA was transiently increased during early lactation, indicating that enhanced hepatic gluconeogenesis during this period may be tied to enhanced capacity for cytosolic rather than mitochondrial formation of phosphoenolpyruvate.
...
PMID:Cloning and characterization of bovine cytosolic and mitochondrial PEPCK during transition to lactation. 1238 98

Perturbations in glucose metabolism in the fetus and in the neonate are a consistent finding in several different animal models of intrauterine growth retardation (IUGR) as well as in humans. Studies in rats who have undergone IUGR have shown decreased hepatic glycogen stores in the fetus and delayed induction of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) at birth. Hepatic transcription factors CCAAT enhancer binding protein (C/EBP)alpha and C/EBPbeta and the increase in cyclic AMP at birth have been implicated in the initial appearance of PEPCK-C. We have examined the effect of IUGR induced by reduced maternal inspired oxygen (fractional inspired oxygen concentration 0.14) on a) the expression of genes for hepatic C/EBPalpha, C/EBPbeta, PEPCK-C and glycogen synthase; and b) transcription of the genes for C/EBPbeta and PEPCK-C by dibutyryl cyclic AMP in the fetus. Three days (d 18-21) of decrease in maternal inspired oxygen resulted in lower maternal arterial PO(2) and a lower birth weight of the pups (p < 0.01). Fetuses that underwent IUGR had significantly lower concentrations of plasma glucose, hepatic glycogen, and glycogen synthase mRNA and a higher hepatic lactate:pyruvate ratio. They also had lower levels of hepatic PEPCK-C mRNA at birth. The concentration of hepatic mRNA for C/EBPalpha and C/EBPbeta as well as the transcription factors themselves were not affected by the decreased maternal inspired oxygen. Fetal injection of dibutyryl cyclic AMP after 24 h of decreased maternal inspired oxygen (d 18-19) had no effect on the expression of C/EBPbeta. However, it resulted in an attenuated induction of PEPCK-C in the fetuses with IUGR. We speculate that a decrease in maternal inspired oxygen induced certain mediators, either in the mother or in the placenta, that caused lower fetal glucose concentration and affected the transcription of genes involved in fetal hepatic glucose metabolism. IUGR, as a result of decreased fractional inspired oxygen concentration may also be the consequence of pH-mediated changes in uterine blood flow. However, these remain to be examined in this experimental model.
...
PMID:Effect of reduced maternal inspired oxygen on hepatic glucose metabolism in the rat fetus. 1253 94

The cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK-C) gene is selectively expressed in several tissues, primarily in the liver, kidney, and adipose tissue. The transcription of the gene is reciprocally regulated by glucocorticoids in these tissues. It is induced in the liver and kidney but repressed in the white adipose tissue. To elucidate which adipocyte-specific transcription factors participate in the repression of the gene, DNase I footprinting analyses of nuclear proteins from 3T3-F442A adipocytes and transient transfection experiments in NIH3T3 cells were utilized. Glucocorticoid treatment slightly reduced the nuclear C/EBP alpha concentration but prominently diminished the binding of adipocyte-derived nuclear proteins to CCAAT/enhancer-binding protein (C/EBP) recognition sites, without affecting the binding to nuclear receptor sites in the PEPCK-C gene promoter. Of members of the C/EBP family of transcription factors, C/EBP alpha was the strongest trans-activator of the PEPCK-C gene promoter in the NIH3T3 cell line. The glucocorticoid receptor (GR), in the presence of its hormone ligand, inhibited the activation of the PEPCK-C gene promoter by C/EBP alpha or C/EBP beta but not by the adipocyte-specific peroxisome proliferator-activated receptor gamma 2. This inhibition effect was similar using the wild type or mutant GR and did not depend on GR binding to the DNA. The glucocorticoid response unit (GRU) in the PEPCK-C gene promoter (-2000 to +73) restrained C/EBP alpha-mediated trans-activation, because mutation of each single GRU element increased this activation by 3-4-fold. This series of GRU mutations were repressed by wild type GR to the same percent as was the nonmutated PEPCK-C gene promoter. In contrast, the repression by mutant GR depended on the intact AF1 site in the gene promoter, whereby mutation of the AF1 element abolished the repression.
...
PMID:Glucocorticoids repress transcription of phosphoenolpyruvate carboxykinase (GTP) gene in adipocytes by inhibiting its C/EBP-mediated activation. 1256 Mar 25

The transcription of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C) gene is differentially regulated in each of the several PEPCK-C-expressing tissues. In the kidney, it is regulated by glucocorticoids and acidosis. Previously, we reported that in LLC-PK1 and derived kidney cell lines, mutation of the hepatic nuclear factor 1 (HNF-1) binding site in PEPCK-C gene promoter markedly reduced both the basal activity of the gene promoter and its response to acidic pH. Using the same kidney cell line, we now report that nuclear receptors robustly stimulate transcription from the PEPCK-C gene promoter. This stimulation is markedly reduced by mutation of the accessory factor 1 (AF1) site in the glucocorticoid responsive unit (GRU) residing within the glucocorticoid-responsive domain. The stimulation is likewise reduced by mutation of the HNF-1 site, residing outside the nuclear receptor-responsive domain of the PEPCK-C gene promoter. There is no binding similarity between HNF-1 and AF1 binding sites, as is evident from gel shift assays showing a lack of competition of either site for the binding of renal nuclear proteins to the other. We further assessed that the regulation of PEPCK-C gene transcription by acidosis is not mediated by nuclear receptors. This became evident from studies of transgenic mice harboring a rat PEPCK-C transgene driven by truncated 5' flanking region of the gene, which contains the HNF-1 site but lacks the glucocorticoid responsive domain. The full transcriptional response of this transgene to acidosis establishes that the truncated 5' flanking region (362 bp) of the PEPCK-C gene contains the information required for the acidosis-mediated regulation independent of the glucocorticoid domain. Taking together the previous and present results, it appears that acidosis and nuclear receptors regulate the renal transcription of the PEPCK-C gene via two independent domains in the 5' flanking region of the gene. These two modulations, as well as the basal activity of the gene, require intact HNF-1 binding site in the gene promoter.
...
PMID:The transcriptional regulation of phosphoenolpyruvate carboxykinase gene in the kidney requires the HNF-1 binding site of the gene. 1458 10

White Leghorn chickens from a nonselected closed population were typed for two RFLP located in the 3' end of the gene coding for cytosolic phosphoenol-pyruvate carboxykinase (PEPCK-C), a major control gene of gluconeogenesis. The two RFLP gave rise to three alleles (or haplotype classes), thus defining six genotypes. Feed efficiency (FE) and residual feed consumption (RFC) varied significantly among the genotypes and indicated that all three haplotypes differed from each other. FE is the ratio between feed consumption and egg mass produced, whereas RFC is the feed consumption after correcting for BW and egg production. There was significant interaction between PEPCK-C genotypes and mitochondrial PEPCK (PEPCK-M) genotypes defined by a single RFLP. The latter enzyme catalyzes the same reaction but is located in the matrix of the mitochondria and is encoded by a different nuclear gene. Interaction was evident from an analysis of the egg weight and egg specific gravity in the early phase of egg laying. It was such that the effect of the variation in one gene depended entirely on the genotype of the second gene. In addition, significant genotypic disequilibria were observed between two of the three alleles of PEPCK-C and between one of these alleles and the two RFLP alleles of PEPCK-M. This finding indicates variations of genes in the gluconeogenesis pathway may affect feed utilization and egg production traits, as well as reproductive fitness.
...
PMID:Alleles of cytosolic phosphoenolpyruvate carboxykinase (PEPCK): trait association and interaction with mitochondrial PEPCK in a strain of White Leghorn chickens. 1465 65

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.
...
PMID:Regulation of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes. 1473 72


1 2 3 4 5 6 Next >>

---