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

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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)

Evidence is presented which suggests that Methylobacterium organophilum contains isoenzymes of phosphoenolpyruvate carboxylase activity. Methanol-grown cells contained an acetyl coenzyme A (CoA)-insensitive activity which precipitated in a 65 to 75% of saturation ammonium sulfate fraction. Succinate-grown cells contained an acetyl-CoA-stimulated activity which precipitated in a 55 to 65% of saturation ammonium sulfate fraction. Mutants unable to grow on methanol appeared to lack acetyl-CoA-insensitive activity. This acetyl-CoA-insensitive phosphoenolpyruvate carboxylase, along with malyl-CoA lyase, is proposed to be encoded by the C-1 operon. The gene for formate dehydrogenase appeared to reside outside the operon and was not inducible by methanol. M. organophilum was unable to grow on formate, and evidence is presented suggesting that formate is unable to induce the enzymes which comprise the serine pathway for formaldehyde fixation. An expanded model for the C-1 operon is presented.
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PMID:Extension of the model concerning linkage of genes coding for C-1 related functions in Methylobacterium organophilum. 678 18

Methylobacterium extorquens AM1 is a facultative methylotrophic bacterium that uses the serine pathway for formaldehyde incorporation as its assimilation pathway during growth on one-carbon compounds. A DNA region from M. extorquens AM1 previously shown to contain genes for the serine pathway enzymes malyl coenzyme A (CoA) lyase and hydroxypyruvate reductase has been characterized in more detail. Insertion mutagenesis revealed an additional region required for growth on one-carbon compounds, and all of the insertion mutants in this region lacked activity for another serine pathway enzyme, the acetyl-CoA-independent phosphoenolpyruvate (PEP) carboxylase. Expression analysis with Escherichia coli of DNA fragments that included the malyl-CoA lyase and PEP carboxylase regions identified five polypeptides, all transcribed in the same direction. Three of these polypeptides were expressed from the region necessary for the acetyl-CoA-independent PEP carboxylase, one was expressed from the region containing the malyl-CoA lyase gene, and the fifth was expressed from a region immediately downstream from the gene encoding hydroxypyruvate reductase. All six genes are transcribed in the same direction, but the transposon insertion data suggest that they are not all cotranscribed.
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PMID:Genetics of serine pathway enzymes in Methylobacterium extorquens AM1: phosphoenolpyruvate carboxylase and malyl coenzyme A lyase. 850 32

It has been proposed that during growth under anaerobic or oxygen-limited conditions, Shewanella oneidensis MR-1 uses the serine-isocitrate lyase pathway common to many methylotrophic anaerobes, in which formaldehyde produced from pyruvate is condensed with glycine to form serine. The serine is then transformed through hydroxypyruvate and glycerate to enter central metabolism at phosphoglycerate. To examine its use of the serine-isocitrate lyase pathway under anaerobic conditions, we grew S. oneidensis MR-1 on [1-13C]lactate as the sole carbon source, with either trimethylamine N-oxide (TMAO) or fumarate as an electron acceptor. Analysis of cellular metabolites indicated that a large percentage (>70%) of lactate was partially oxidized to either acetate or pyruvate. The 13C isotope distributions in amino acids and other key metabolites indicate that under anaerobic conditions, although glyoxylate synthesized from the isocitrate lyase reaction can be converted to glycine, a complete serine-isocitrate pathway is not present and serine/glycine is, in fact, oxidized via a highly reversible degradation pathway. The labeling data also suggest significant activity in the anapleurotic (malic enzyme and phosphoenolpyruvate carboxylase) reactions. Although the tricarboxylic acid (TCA) cycle is often observed to be incomplete in many other anaerobes (absence of 2-oxoglutarate dehydrogenase activity), isotopic labeling supports the existence of a complete TCA cycle in S. oneidensis MR-1 under certain anaerobic conditions, e.g., TMAO-reducing conditions.
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PMID:Anaerobic central metabolic pathways in Shewanella oneidensis MR-1 reinterpreted in the light of isotopic metabolite labeling. 1711 68

Ignicoccus hospitalis is an autotrophic hyperthermophilic archaeon that serves as a host for another parasitic/symbiotic archaeon, Nanoarchaeum equitans. In this study, the biosynthetic pathways of I. hospitalis were investigated by in vitro enzymatic analyses, in vivo (13)C-labeling experiments, and genomic analyses. Our results suggest the operation of a so far unknown pathway of autotrophic CO(2) fixation that starts from acetyl-coenzyme A (CoA). The cyclic regeneration of acetyl-CoA, the primary CO(2) acceptor molecule, has not been clarified yet. In essence, acetyl-CoA is converted into pyruvate via reductive carboxylation by pyruvate-ferredoxin oxidoreductase. Pyruvate-water dikinase converts pyruvate into phosphoenolpyruvate (PEP), which is carboxylated to oxaloacetate by PEP carboxylase. An incomplete citric acid cycle is operating: citrate is synthesized from oxaloacetate and acetyl-CoA by a (re)-specific citrate synthase, whereas a 2-oxoglutarate-oxidizing enzyme is lacking. Further investigations revealed that several special biosynthetic pathways that have recently been described for various archaea are operating. Isoleucine is synthesized via the uncommon citramalate pathway and lysine via the alpha-aminoadipate pathway. Gluconeogenesis is achieved via a reverse Embden-Meyerhof pathway using a novel type of fructose 1,6-bisphosphate aldolase. Pentosephosphates are formed from hexosephosphates via the suggested ribulose-monophosphate pathway, whereby formaldehyde is released from C-1 of hexose. The organism may not contain any sugar-metabolizing pathway. This comprehensive analysis of the central carbon metabolism of I. hospitalis revealed further evidence for the unexpected and unexplored diversity of metabolic pathways within the (hyperthermophilic) archaea.
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PMID:Insights into the autotrophic CO2 fixation pathway of the archaeon Ignicoccus hospitalis: comprehensive analysis of the central carbon metabolism. 1740 Jul 48

The mycobacteria comprise both pathogenic and nonpathogenic bacteria. Although several features related to pathogenicity in various mycobacterial species, such as Mycobacterium tuberculosis, have been studied in great detail, methylotrophy, i.e., the ability of an organism to utilize single-carbon (C₁) compounds as the sole source of carbon and energy, has remained largely unexplored in mycobacteria. Reports are available that suggest that mycobacteria, including M. tuberculosis and M. smegmatis, are capable of utilizing alternative C₁ compounds to meet their carbon and energy requirements. However, physiological pathways that are functional in mycobacteria to utilize such carbon compounds are only poorly understood. Here we report the identification and characterization of the gene products required for establishing methylotrophy in M. smegmatis We present N,N-dimethyl-p-nitrosoaniline (NDMA)-dependent methanol oxidase (Mno) as the key enzyme that is essential for the growth of M. smegmatis on methanol. We show that Mno has both methanol and formaldehyde dehydrogenase activities in vitro Further, M. smegmatis is able to utilize methanol even in the absence of the major formaldehyde dehydrogenase MscR, which suggests that Mno is sufficient to dissimilate methanol and the resulting formaldehyde in vivo Finally, we show that M. smegmatis devoid of phosphoenolpyruvate carboxykinase, which has been shown to fix CO₂ in M. tuberculosis, does not grow on methanol, suggesting that the final step of methanol utilization requires CO₂ fixation for biomass generation. Our work here thus forms the first comprehensive report that explores methylotrophy in a mycobacterial species.IMPORTANCE Methylotrophy, the ability to utilize single-carbon (C₁) compounds as the sole carbon and energy sources, is only poorly understood in mycobacteria. Both pathogenic and nonpathogenic mycobacteria, including Mycobacterium tuberculosis, are capable of utilizing C₁ compounds to meet their carbon and energy requirements, although the precise pathways are not well studied. Here we present a comprehensive study of methylotrophy in Mycobacterium smegmatis With several genetic knockouts, we have dissected the entire methanol metabolism pathway in M. smegmatis We show that while methanol dissimilation in M. smegmatis differs from that in other mycobacterial species, the concluding step of CO₂ fixation is similar to that in M. tuberculosis It is therefore both interesting and important to examine mycobacterial physiology in the presence of alternative carbon sources.
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PMID:Methylotrophy in Mycobacteria: Dissection of the Methanol Metabolism Pathway in Mycobacterium smegmatis. 2989 42

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