ArticleThe Journal of biological chemistry2014
Gluconeogenesis in Leishmania mexicana: contribution of glycerol kinase, phosphoenolpyruvate carboxykinase, and pyruvate phosphate dikinase.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 39 citations in OpenAlex.
- Glycosomal Phosphoenolpyruvate Carboxykinase CRISPR/Cas9-Deletion and Its Role in Trypanosoma cruzi Metacyclogenesis and Infectivity in Mammalian Host.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Glycerol biosynthetic pathway plays an essential role in proliferation and antioxidative defense in the human enteric protozoan parasite Entamoeba histolytica.Scientific reports · 2023Article
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- A New Strategy for Mapping Epitopes of LACK and PEPCK Proteins ofInternational journal of molecular sciences · 2023Article
- Aurothiomalate-Based Drugs as Potentially Novel Agents Against Leishmania major: A Mini Review.Acta parasitologica · 2022Review
- Utilizing Quantitative Proteomics to Identify Species-Specific Protein Therapeutic Targets for the Treatment of Leishmaniasis.ACS omega · 2022Article
- Three types ofFrontiers in cellular and infection microbiology · 2022Article
- Distinct features of the Leishmania cap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated hemizygous deletion.PLoS neglected tropical diseases · 2021Article
- SystematicFrontiers in chemistry · 2021Article
- An overview of biochemically characterized drug targets in metabolic pathways of Leishmania parasite.Parasitology research · 2020Review
- Article
- Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei.PLoS pathogens · 2018Article
- Gluconeogenesis is essential for trypanosome development in the tsetse fly vector.PLoS pathogens · 2018Article
- Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana.PLoS pathogens · 2018Article
- Transcriptomic and proteomic analyses of core metabolism in Clostridium termitidis CT1112 during growth on α-cellulose, xylan, cellobiose and xylose.BMC microbiology · 2016Article
- Leishmania carbon metabolism in the macrophage phagolysosome- feast or famine?F1000Research · 2015Review
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Authors and funding
2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Gluconeogenesis is an active pathway in Leishmania amastigotes and is essential for their survival within the mammalian cells. However, our knowledge about this pathway in trypanosomatids is very limited. We investigated the role of glycerol kinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate phosphate dikinase (PPDK) in gluconeogenesis by generating the respective Leishmania mexicana Δgk, Δpepck, and Δppdk null mutants. Our results demonstrated that indeed GK, PEPCK, and PPDK are key players in the gluconeogenesis pathway in Leishmania, although stage-specific differences in their contribution to this pathway were found. GK participates in the entry of glycerol in promastigotes and amastigotes; PEPCK participates in the entry of aspartate in promastigotes, and PPDK is involved in the entry of alanine in amastigotes. Furthermore, the majority of alanine enters into the pathway via decarboxylation of pyruvate in promastigotes, whereas pathway redundancy is suggested for the entry of aspartate in amastigotes. Interestingly, we also found that l-lactate, an abundant glucogenic precursor in mammals, was used by Leishmania amastigotes to synthesize mannogen, entering the pathway through PPDK. On the basis of these new results, we propose a revision in the current model of gluconeogenesis in Leishmania, emphasizing the differences between amastigotes and promastigotes. This work underlines the importance of studying the trypanosomatid intracellular life cycle stages to gain a better understanding of the pathologies caused in humans.
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