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

Abstract

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.