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)

The crucial role of retinoids in controlling differentiation processes has become evident from studies conducted in a variety of in vivo and in vitro systems. Most striking is the role of retinoic acid as a morphogenic substance in vertebrate limb development, but equally important is its role in the maintenance of epithelial integrity in most superficial linings of the body. The similarity of the mode of action of retinoids to that of the steroid and thyroid hormones has recently been demonstrated with the discovery of the nuclear receptors for retinoic acid, which belong to the steroid/thyroid hormone receptor superfamily. These receptors act as transcriptional activators by binding as heterodimers to specific nucleotide sequences in the response elements of target genes. Response elements for retinoic acid have so far been identified for the rat growth hormone and phosphoenolpyruvate carboxykinase, the mouse complement H and laminin B1, the human and mouse retinoic acid receptor beta, the human osteocalcin, and the human alcohol dehydrogenase genes. The retinoic acid response element (RARE) for the rat growth hormone gene is also a thyroid hormone response element (TRE), and the AP-1 binding site of the human osteocalcin promoter is also a vitamin D response element (VDRE) and a RARE. Both these elements are palindromic. Other RAREs have a direct repeat configuration of the half-site motif AGGTCA separated by five nucleotides (AGGTCA xxxxx AGGTCA). The direct repeat arrangement of the same core motif AGGTCA separated by three or four nucleotides becomes a VDRE or TRE, respectively. A point mutation has been identified in the RAR alpha gene of embryonal carcinoma cells resistant to retinoic acid. In addition to the three retinoic acid receptors (alpha, beta, gamma) belonging to the steroid/thyroid hormone receptor superfamily, a second class of retinoid receptors (RXR) alpha, beta, gamma has also been characterized and its relatedness to a gene, XR2C, of the locus ultraspiracle required for pattern formation in Drosophila has been established. That would suggest that both vertebrates and invertebrates may require similar transcriptional activators during morphogenesis. An RXRE has been identified in the CRBPII gene promoter and it contains five repeats of the canonical sequence AGGTCA separated by one nucleotide. The importance of retinoids, both as chemopreventive agents of tumorigenesis and potent differentiation inducers of neoplastic cells, can only be emphasized by the recent finding that the t(15;17) (q21- q11-22) translocation, specifically associated with acute promyelocytic leukemia, also causes translocation of the retinoic acid receptor alpha gene and its fusion with with a new locus, myl, of unknown function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retinoids and their receptors in differentiation, embryogenesis, and neoplasia. 166 Dec 45

A region of 14.2 kb has been analysed that is a part of a locus on the Methylobacterium extorquens AM1 chromosome containing a number of genes involved in one-carbon (C1) metabolism, including serine cycle genes, pqq genes, regulatory methanol oxidation genes and the gene for N5,N10-methylene tetrahydrofolate dehydrogenase (mtdA). Fifteen new ORFs have been identified within the new region, and their sequences suggest that they encode the following polypeptides: the C-terminal part of phosphoenolpyruvate carboxylase, malyl-CoA lyase, polypeptides of 9.4 and 31 kDa of unknown function, three putative subunits of an ABC-type transporter, two polypeptides similar to the products of mxaF and mxaJ from M. extorquens AM1 and other methylotrophs, a cytochrome c, three enzymes of folate metabolism, and polypeptides of 13 and 20.5 kDa with no homologues in the protein database. Ten insertion mutations have been generated in the region to determine if the newly identified genes are associated with C1 metabolism. A mutation in mclA, encoding malyl-CoA lyase, resulted in a C1-minus phenotype, while mutations in the other genes all showed a C1-plus phenotype. It was not possible to obtain null mutants in a putative folate metabolism gene, folC, implying the necessity of these folate synthesis genes for metabolism of C1 and multicarbon compounds. Mutations in the putative ABC transporter genes, the genes similar to mxaG and mxaJ, and other unidentified ORFs produced double-crossover recombinants with a C1-positive phenotype. Promoter regions have been investigated upstream of orf3 and orf4 using the promoter probe vector pHX200. Transcription from these promoters was weak in wild-type M. extorquens AM1 but increased in regulatory mox mutants.
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PMID:Molecular and mutational analysis of a DNA region separating two methylotrophy gene clusters in Methylobacterium extorquens AM1. 916 22

To monitor the global gene expression of Corynebacterium glutamicum we established two formats of DNA-arrays on nylon membranes. We produced an ordered DNA-array of PCR fragments from a shotgun library of C. glutamicum representing a threefold coverage of the genome. With this format we studied genome-wide transcriptional changes after heat shock. Sequence and subsequent BLAST analysis of PCR fragments with elevated expression after heat shock revealed PCR fragments harboring genes that encode several proteins of the heat shock family, proteins of the oxidative stress response and proteins with unknown function. DNA-arrays based on PCR fragments representing 2804 annotated ORFs of C. glutamicum were used to monitor the transcript levels during growth on acetate and glucose. We determined minimal detectable ratios and compared labeling approaches with random hexamers and ORF-specific primers. ORF-based DNA-array analysis with different labeling approaches showed similar results: e.g. increased mRNA levels of the pta-ack operon, aceA, aceB and genes encoding phosphoenolpyruvate carboxykinase and enzymes of the citric acid cycle during growth on acetate and elevated mRNA levels of some enzymes of the glycolytic pathway and lactate dehydrogenase upon growth on glucose. These results demonstrate that shotgun DNA-arrays and ORF-based DNA-arrays are appropriate tools to study physiology of microorganism.
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PMID:Genome-wide transcription profiling of Corynebacterium glutamicum after heat shock and during growth on acetate and glucose. 1214 91

The amino acid producing Corynebacterium glutamicum grows aerobically on a variety of carbohydrates and organic acids as single or combined sources of carbon and energy. Among the substrates metabolized are glucose and acetate which both can also serve as substrates for amino acid production. Based on biochemical, genetic and regulatory studies and on quantitative determination of metabolic fluxes during utilization of acetate and/or glucose, this review summarizes the present knowledge on the different steps of the fundamental pathways of acetate utilization in C. glutamicum, namely, on acetate transport, acetate activation, tricarboxylic acid (TCA) cycle, glyoxylate cycle and gluconeogenesis. It becomes evident that, although the pathways of acetate utilization follow the same theme in many bacteria, important biochemical, genetic and regulatory peculiarities exist in C. glutamicum. Recent genome wide and comparative expression analyses in C. glutamicum cells grown on glucose and on acetate substantiated previously identified transcriptional regulation of acetate activating enzymes and of glyoxylate cycle enzymes. Additionally, a variety of genes obviously also under transcriptional control in response to the presence or absence of acetate in the growth medium were uncovered. These genes, thus also belonging to the acetate stimulon of C. glutamicum, include genes coding for TCA cycle enzymes (e.g. aconitase and succinate dehydrogenase), for gluconeogenesis (phosphoenolpyruvate carboxykinase), for glycolysis (pyruvate dehydrogenase E1) and genes coding for proteins with hitherto unknown function. Although the basic mechanism of transcriptional regulation of the enzymes involved in acetate metabolism is not yet understood, some recent findings led to a better understanding of the adaptation of C. glutamicum to acetate at the molecular level.
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PMID:Acetate metabolism and its regulation in Corynebacterium glutamicum. 1294 33

Detached roots and nodules of the N(2)-fixing species, Albus glutinosa (European black alder), actively assimilate CO(2). The maximum rates of dark CO(2) fixation observed for detached nodules and roots were 15 and 3 micromoles CO(2) fixed per gram dry weight per hour, respectively. The net incorporation of CO(2) in these tissues was catalyzed by phosphoenolpyruvate carboxylase which produces organic acids, some of which are used in the synthesis of the amino acids, aspartate, glutamate, and citrulline and by carbamyl phosphate synthetase. The latter accounts for approximately 30 to 40% of the CO(2) fixed and provides carbamyl phosphate for the synthesis of citrulline. Results of labeling studies suggest that there are multiple pools of malate present in nodules. The major pool is apparently metabolically inactive and of unknown function while the smaller pool is rapidly utilized in the synthesis of amino acids. Dark CO(2) fixation and N(2) fixation in nodules decreased after treatment of nodulated plants with nitrate while the percentage of the total (14)C incorporated into organic acids increased. Phosphoenolpyruvate carboxylase and carbamyl phosphate synthetase play key roles in the synthesis of amino acids including citrulline and in the metabolism of N(2)-fixing nodules and roots of alder.
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PMID:Carbon Dioxide Fixation in Roots and Nodules of Alnus glutinosa: I. Role of Phosphoenolpyruvate Carboxylase and Carbamyl Phosphate Synthetase in Dark CO(2) Fixation, Citrulline Synthesis, and N(2) Fixation. 1666 82

Sugarcane (Saccharum spp.) is a highly efficient biomass and sugar producing crop. Leaf reactions have been considered as potential rate-limiting step for sucrose accumulation in sugarcane stalks. To characterize the sugarcane leaf transcriptome, field-grown mature leaves from cultivar "SP80-3280" were analyzed using Serial Analysis of Gene Expression (SAGE). From 480 sequenced clones, 9,482 valid tags were extracted, with 5,227 unique sequences, from which 3,659 (70%) matched at least a sugarcane assembled sequence (SAS) with putative function; while 872 tags (16.7%) matched SAS with unknown function; 523 (10%) matched SAS without a putative annotation; and only 173 (3.3%) did not match any sugarcane ESTs. Based on gene ontology (GO), photosystem (PS) I reaction center was identified as the most frequent gene product location, followed by the remaining sites of PS I, PS II and thylakoid complexes. For metabolic processes, photosynthesis light harvesting complexes; carbon fixation; and chlorophyll biosynthesis were the most enriched GO-terms. Considering the alternative photosynthetic C(4) cycles, tag frequencies related to phosphoenolpyruvate carboxykinase (PEPCK) and aspartate aminotransferase compared to those for NADP(+)-malic enzyme (NADP-ME) and NADP-malate dehydrogenase, suggested that PEPCK-type decarboxylation appeared to predominate over NADP-ME in mature leaves, although both may occur, opposite to currently assumed in sugarcane. From the unique tag set, 894 tags (17.1%) were assigned as potentially derived from antisense transcripts, while 73 tags (1.4%) were assigned to more than one SAS, suggesting the occurrence of alternative processing. The occurrence of antisense was validated by quantitative reverse transcription amplification. Sugarcane leaf transcriptome provided new insights for functional studies associated with sucrose synthesis and accumulation.
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PMID:Serial analysis of gene expression in sugarcane (Saccharum spp.) leaves revealed alternative C4 metabolism and putative antisense transcripts. 1721 12

Central metabolism is a topic that has been studied for decades, and yet, this process is still not fully understood in Escherichia coli, perhaps the most amenable and well-studied model organism in biology. To further our understanding, we used a high-throughput method to measure the growth kinetics of each of 3,796 E. coli single-gene deletion mutants in 30 different carbon sources. In total, there were 342 genes (9.01%) encompassing a breadth of biological functions that showed a growth phenotype on at least 1 carbon source, demonstrating that carbon metabolism is closely linked to a large number of processes in the cell. We identified 74 genes that showed low growth in 90% of conditions, defining a set of genes which are essential in nutrient-limited media, regardless of the carbon source. The data are compiled into a Web application, Carbon Phenotype Explorer (CarPE), to facilitate easy visualization of growth curves for each mutant strain in each carbon source. Our experimental data matched closely with the predictions from the EcoCyc metabolic model which uses flux balance analysis to predict growth phenotypes. From our comparisons to the model, we found that, unexpectedly, phosphoenolpyruvate carboxylase (ppc) was required for robust growth in most carbon sources other than most trichloroacetic acid (TCA) cycle intermediates. We also identified 51 poorly annotated genes that showed a low growth phenotype in at least 1 carbon source, which allowed us to form hypotheses about the functions of these genes. From this list, we further characterized the ydhC gene and demonstrated its role in adenosine efflux.IMPORTANCE While there has been much study of bacterial gene dispensability, there is a lack of comprehensive genome-scale examinations of the impact of gene deletion on growth in different carbon sources. In this context, a lot can be learned from such experiments in the model microbe Escherichia coli where much is already understood and there are existing tools for the investigation of carbon metabolism and physiology (1). Gene deletion studies have practical potential in the field of antibiotic drug discovery where there is emerging interest in bacterial central metabolism as a target for new antibiotics (2). Furthermore, some carbon utilization pathways have been shown to be critical for initiating and maintaining infection for certain pathogens and sites of infection (3-5). Here, with the use of high-throughput solid medium phenotyping methods, we have generated kinetic growth measurements for 3,796 genes under 30 different carbon source conditions. This data set provides a foundation for research that will improve our understanding of genes with unknown function, aid in predicting potential antibiotic targets, validate and advance metabolic models, and help to develop our understanding of E. coli metabolism.
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PMID:Gene Dispensability in Escherichia coli Grown in Thirty Different Carbon Environments. 3320 62