Gluconeogenesis in Leishmania mexicana

Rodriguez‐Contreras, Dayana; Hamilton, Nicklas

doi:10.1074/jbc.m114.569434

Cited by 38 publications

(21 citation statements)

References 52 publications

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“…In C. thermocellum , PPDK was similarly found to be up regulated on α-cellulose at stationary phase compared to cellobiose [ 7 ]. PPDK plays an anabolic role in gluconeogenesis in some organisms [ 43 , 44 ], and functions in the catabolic direction in others [ 40 , 45 ]. As has been shown in Thermoproteus tenax [ 40 ], the simultaneous presence and expression of PPDK with PPK in C. termitidis may represent allosteric differential regulation, thereby providing a way in controlling the inter-conversion of phosphoenolpyruvate and pyruvate and allowing adaptation to different conditions.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic and proteomic analyses of core metabolism in Clostridium termitidis CT1112 during growth on α-cellulose, xylan, cellobiose and xylose

et al. 2016

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BackgroundClostridium termitidis CT1112 is an anaerobic, Gram-positive, mesophilic, spore-forming, cellulolytic bacterium, originally isolated from the gut of a wood feeding termite Nasusitermes lujae. It has the ability to hydrolyze both cellulose and hemicellulose, and ferment the degradation products to acetate, formate, ethanol, lactate, H2, and CO2. It is therefore ges in gene and gene product expression during growth of C. termitidis on cellobiose, xylose, xylan, and α–cellulose.ResultsCorrelation of transcriptome and proteome data with growth and fermentation profiles identified putative carbon-catabolism pathways in C. termitidis. The majority of the proteins associated with central metabolism were detected in high abundance. While major differences were not observed in gene and gene-product expression for enzymes associated with metabolic pathways under the different substrate conditions, xylulokinase and xylose isomerase of the pentose phosphate pathway were found to be highly up-regulated on five carbon sugars compared to hexoses. In addition, genes and gene-products associated with a variety of cellulosome and non-cellulosome associated CAZymes were found to be differentially expressed. Specifically, genes for cellulosomal enzymes and components were highly expressed on α–cellulose, while xylanases and glucosidases were up-regulated on 5 carbon sugars with respect to cellobiose. Chitinase and cellobiophosphorylases were the predominant CAZymes expressed on cellobiose. In addition to growth on xylan, the simultaneous consumption of two important lignocellulose constituents, cellobiose and xylose was also demonstrated.ConclusionThere are little changes in core-metabolic pathways under the different carbon sources compared. The most significant differences were found to be associated with the CAZymes, as well as specific up regulation of some key components of the pentose phosphate pathway in the presence of xylose and xylan. This study has enhanced our understanding of the physiology and metabolism of C. termitidis, and provides a foundation for future studies on metabolic engineering to optimize biofuel production from natural biomass.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0711-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic and proteomic analyses of core metabolism in Clostridium termitidis CT1112 during growth on α-cellulose, xylan, cellobiose and xylose

et al. 2016

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“…An earlier study of carbon metabolism reported by Saunders and colleagues, revealed glucose to be the dominant carbon source with aspartate also entering the TCA cycle but other amino acids or fatty acids having little or no role [ 2 ]. Another study, however, indicated that utilisation of amino acids for mannogen biogenesis was highly dependent upon the presence or absence of glucose in the culture medium [ 39 ]. Following the distribution of carbons from labelled glucose here we confirmed that glucose is the main carbon source for the TCA cycle in WT parasites under standard culture conditions.…”

Section: Discussionmentioning

confidence: 99%

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Kovářová¹,

Pountain²,

Wildridge³

et al. 2018

PLoS Pathog

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Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not virulent in mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased two-fold in the knock-out cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both.

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“…38 In these processes, glucose and other hexoses are critical cellular nutrients to Leishmania parasites, where these parasites (promastigote or amastigote life form) are able to import sugar from the extracellular environment or synthesize de novo, via gluconeogenesis. 39 Promastigote parasites made both process, but amastigote parasites only carry out gluconeogenesis process. 39 Glyceraldehyde 3-phosphate dehydrogenase Leishmania major (PDB ID: 1GYP and 1A7K, see Fig.…”

Section: Oxidoreductases (Ec 1)mentioning

confidence: 99%

“…39 Promastigote parasites made both process, but amastigote parasites only carry out gluconeogenesis process. 39 Glyceraldehyde 3-phosphate dehydrogenase Leishmania major (PDB ID: 1GYP and 1A7K, see Fig. 4) belongs to oxidoreductase group and participate in Pentose Phosphate and glycolysis metabolic pathways.…”

Section: Oxidoreductases (Ec 1)mentioning

confidence: 99%

<em>Leishmania</em> Proteomics: An <em>in Silico</em> Perspective

Padilla¹,

Álvarez²,

Combariza³

2020

Preprint

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We report on the state of the art of scientific literature about proteins recognized as potential targets for the development of Leishmania treatments through the search of biologically active chemical species, either from experimental in vitro, in vivo, or in silico sources. We classify the gathered information, in several ways: vector taxonomy and geographical distribution, parasite taxonomic and geographical distribution and enzymatic function (oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and cytokines). Our aim is to provide a much needed reference layout for research efforts aimed to understand the underpinning physical interactions in ligand-protein activation/inactivation processes. In the specific case of Leishmania, we focus on enzymes known to be part of the biochemical molecular processes initiated following a Leishmania infectious episode.

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Gluconeogenesis in Leishmania mexicana

Cited by 38 publications

References 52 publications

Transcriptomic and proteomic analyses of core metabolism in Clostridium termitidis CT1112 during growth on α-cellulose, xylan, cellobiose and xylose

Transcriptomic and proteomic analyses of core metabolism in Clostridium termitidis CT1112 during growth on α-cellulose, xylan, cellobiose and xylose

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

<em>Leishmania</em> Proteomics: An <em>in Silico</em> Perspective

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