Glutathione and protein thiol redox system (Plasmodium) (GSH/Protein-SH system)

The glutathione and protein thiol system in Plasmodium is a critical metabolic network responsible for maintaining redox equilibrium within the malaria parasite during its development inside host red blood cells. As the parasite consumes host hemoglobin, it releases large quantities of pro-oxidant heme and generates reactive oxygen species (ROS), making a robust antioxidant defense essential for its survival (Müller et al., 2003, PMID: 12831601). Glutathione (GSH) serves as the primary low-molecular-weight thiol that neutralizes ROS and maintains protein thiols in their functional reduced state, a process regulated by enzymes like glutathione reductase (GR) and glutamate-cysteine ligase (GCL) (Sarma et al., 2003, PMID: 12623524). Pharmacological targeting of this system, using agents such as methylene blue or buthionine sulfoximine, disrupts the parasite's ability to manage oxidative stress, leading to cellular damage and death (Becker et al., 2004, PMID: 15121182). While it is a promising therapeutic target, the high degree of similarity between parasite and host redox enzymes poses a significant challenge for achieving drug selectivity and avoiding host toxicity (Luersen et al., 2000, PMID: 10896311).

Other names

Plasmodium glutathione metabolismThiol-based antioxidant system of PlasmodiumGSH/GSSG redox couplePlasmodium falciparum glutathione system

Inhibition of glutathione-dependent enzymes such as glutathione reductase and glutamate-cysteine ligase, or direct depletion of the reduced glutathione pool, leading to the accumulation of reactive oxygen species and lethal oxidative stress in the parasite.