Characteristics of Plasmodium vivax apicomplexan amino acid transporter 8 (PvApiAT8) in the cationic amino acid transport.

Plasmodium vivax is the most widespread malaria parasite affecting humans, and its eradication is challenging due to the spread of drug-resistant parasites and their ability to remain in liver as a dormant stage. These parasites invade and multiply extensively within hepatocytes and erythrocytes in the host, relying on nutrient acquisition for their growth and replication. A promising new treatment aimed at targeting P. vivax involves blocking cationic amino acid uptake, which is a biological source of nutrients for the parasite. Novel Putative Transporter 1 (NPT1), identified as a cationic amino acid transporter in Apicomplexan, has a homologue in Plasmodium species known as apicomplexan amino acid transporter 8 (ApiAT8). This study focuses on P. vivax ApiAT8 to understand its precise role. PvApiAT8 was expressed in Xenopus laevis oocytes and shown to selectively uptake cationic amino acids. The uptake activity of [(3)H] L-arginine was shown to depend on PvApiAT8 expression time and substrate incubation time. PvApiAT8 was sodium-independent and functioned at pH levels between 6.5 and 8.5, with no efflux activity observed. Kinetic analysis showed saturable uptake for L-arginine consistent with Michaelis-Menten kinetics, with a Km of 1.5 ± 0.3 µM and a Vmax of 25.0 ± 4.8 pmol/oocyte/hr. Inhibition assays further confirmed its selectivity for cationic amino acids such as L-arginine, L-lysine, L-histidine, and L-ornithine. Sequence and structural analyses revealed a conserved binding pocket for cationic amino acids in Plasmodium species, distinct from that in Toxoplasma gondii NPT1. These findings highlight the potential of targeting PvApiAT8 in developing new treatments for P. vivax malaria.