Girard, R. M. B. M. | bioRxiv Science

bioRxiv2024

Elucidating the Transport Mechanisms and Metabolic Roles of Serine, Threonine, and Glycine in Trypanosoma cruzi

O_SCPLOWLC_SCPLOW-Serine (O_SCPLOWLC_SCPLOW-Ser) and O_SCPLOWLC_SCPLOWO_SCPCAP-C_SCPCAPThreonine (O_SCPLOWLC_SCPLOWO_SCPCAP-C_SCPCAPThr) have versatile roles in metabolism. In addition to their use in protein synthesis, these amino acids participate in the biosynthesis pathways of other amino acids and even phospholipids. Furthermore, O_SCPLOWLC_SCPLOW-Ser and O_SCPLOWLC_SCPLOWO_SCPCAP-C_SCPCAPThr can be substrates for a Ser/Thr dehydratase (Ser/ThrDH), resulting in pyruvate (Pyr) and 2-oxobutyrate, respectively, thus being amino acids with anaplerotic potential. Trypanosoma cruzi, the etiological agent of Chagas disease, uses amino acids in several biological processes: metacyclogenesis, infection, resistance to nutritional and oxidative stress, osmotic control, etc. In this study, we investigated the import and metabolism of O_SCPLOWLC_SCPLOW-Ser, O_SCPLOWLC_SCPLOWO_SCPCAP-C_SCPCAPThr, and Gly in T. cruzi. Our results demonstrate that these amino acids are transported from the extracellular environment into T. cruzi cells through a saturable transport system that fits the Michaelis-Menten model. Our results show that O_SCPLOWLC_SCPLOW-Ser and O_SCPLOWLC_SCPLOWO_SCPCAP-C_SCPCAPThr can sustain epimastigote (Epi) cell viability under nutritional stress (NS) conditions and can stimulate oxygen consumption to maintain intracellular ATP levels. Additionally, our findings indicate that O_SCPLOWLC_SCPLOW-Ser plays a role in establishing the mitochondrial membrane potential ({Delta}{Psi}m) in T. cruzi. O_SCPLOWLC_SCPLOW-Ser is also involved in energy metabolism via the Ser-Pyr pathway, which stimulates the production and subsequent excretion of acetate and alanine. Our results demonstrate the importance of O_SCPLOWLC_SCPLOW-Ser and O_SCPLOWLC_SCPLOW-Thr in the energy metabolism of T. cruzi and provide new insights into the metabolic adaptations of this parasite during its life cycle.

biochemistry↗

bioRxiv2023

How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell

ATP hydrolysis is required for the synthesis, transport and polymerization of monomers for macromolecules as well as for the assembly of the latter into cellular structures. Other cellular processes not directly related to synthesis of biomass, such as maintenance of membrane potential and cellular shape, also require ATP. The unicellular flagellated parasite Trypanosoma brucei has a complex digenetic life cycle. The primary energy source for this parasite in its bloodstream form (BSF) is glucose, which is abundant in the hosts bloodstream. Here, we made a detailed estimation of the energy budget during the BSF cell cycle. As glycolysis is the source of most produced ATP, we calculated that a single parasite produces 6x1011 molecules of ATP/cell cycle. Biomass production accounts for [~]62% of the total energy budget, with translation being the most expensive process. Flagellar motility, variant surface glycoprotein recycling, transport and maintenance of transmembrane potential account for less than 30% of the consumed ATP. Finally, there is still [~]9% available in the budget that is being used for other cellular processes of unknown cost. These data put a new perspective on the assumptions about the relative energetic weight of the processes a BSF trypanosome undergoes during its cell cycle. Abstract ImportanceCells use ATP as the main energy currency for the synthesis, organization and maintenance of their macromolecules and cellular structures, in order to stay alive and proliferate. For this purpose, ATP is produced from external nutrients, and is spent by cells in the many processes that are necessary for maintenance and building up new cells. Despite its relevance and the impressive quantity of biological data available, very little is known about how much ATP is required for maintaining and duplicating a cell. In this paper, we present a calculation on how much of the ATP produced by catabolism of the nutrient glucose is used to energize the different processes known to occur during the cell cycle of the infective form of the trypanosomatid parasite that causes human sleeping sickness, the bloodstream form of Trypanosoma brucei.

biochemistry↗