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Full-Text Articles in Biochemistry

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman Dec 2023

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

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The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …


Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama Aug 2023

Fatty Acids And Parasitism: Towards A Better Understanding Of Lipid Metabolism In Trypanosoma Brucei, Joshua Saliutama

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Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and cattle. As an extracellular parasite, T. brucei relies on the host’s nutrients to satisfy its growth requirements. The parasite is unusual because it does not uptake most of the host’s lipid species. Instead, T. brucei prefers to perform de novo synthesis of most lipid species. One of the lipid species that T. brucei can both uptake and synthesize is fatty acids. In my thesis work, I investigated the dynamics of fatty acid uptake, metabolism, and utilization of T. brucei. My work starts by determining the …


Characterization Of A Potential Glucose Transporter In Trypanosoma Brucei, Matthew Morgan May 2022

Characterization Of A Potential Glucose Transporter In Trypanosoma Brucei, Matthew Morgan

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Trypanosoma brucei, the African trypanosome, is an organism heavily dependent on glucose for ATP production during the infectious stage of its life cycle. Here, we have explored the role of an uncharacterized protein designated “novel glucose transporter” (NGT) as a potential glucose transporter. Sequence analyses suggests that NGT shares similarities (either at the primary sequence level or structurally) with Trypanosome Hexose Transporters 1 (TbTHT1), and human GLUT3, both of which are membrane sugar transporters. NGT was localized by fluorescence microscopy to subcellular structures consistent with lysosomes. Silencing NGT expression with RNA interference in parasites resulted in a growth defect …


Regulation Of Trypanosoma Brucei Hexokinase 1 And 2 On Multiple Levels: Transcript Abundance, Protein Expression And Enzyme Activity, Heidi Dodson May 2011

Regulation Of Trypanosoma Brucei Hexokinase 1 And 2 On Multiple Levels: Transcript Abundance, Protein Expression And Enzyme Activity, Heidi Dodson

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Trypanosoma brucei, a unicellular eukaryotic parasite, is the causative agent of African sleeping sickness in sub-Saharan Africa. The parasite encounters two main environments as it progresses through its life cycle: the tsetse fly and the mammalian
bloodstream. Nutrient availability is distinct in the two environments, requiring the parasite to utilize diverse metabolic pathways to efficiently produce ATP for survival. Bloodstream form parasites (BSF), residing in a glucose rich environment, rely solely on
glycolysis for energy, while procyclic form (PF) parasites metabolize readily available proline and threonine in addition to glucose.
T. brucei expresses two hexokinases, the first enzyme in the …