(1) GSH biosynthesis is facilitated by γ-glutamyl cysteine synthase (PfGCS) and glutathione synthase (PfGS). (2) The cytosolic defense system encompasses key components like GSH thioredoxin (PfTrx1), thioredoxin reductase (PfTrxR), glutathione reductase (PfGR), cytosolic superoxide dismutase (PfSOD1), thioredoxin-like protein (PfTlp1), as well as glutaredoxin and glutaredoxin-like proteins (PfGrx1, PfGlp1&2), plasmoredoxin (PfPlx), and thioredoxin-dependent peroxidase (PfTpx1 or PfTpxGI). GSH conjugates, along with oxidized glutathione (GSSG), are transported to the host cell via the GSSG pump known as MRP (PfMRP, multidrug resistance-associated protein). (3) NADPH + H+ acts as the primary electron source for redox reactions and is primarily generated through the action of the pentose phosphate pathway (PPP) and glutamate dehydrogenase. (4) The glyoxalase system is responsible for detoxifying 2-ketoaldehydes. (5) Mitocho-ndrial antioxidant and redox systems. (6) Apicoplast antioxidant and redox system. (7) Oxidative protein folding and redox reactions in the endoplasmic reticulum. (8) The parasite employs specialized survival strategies to adapt to oxidative stress.

Pal C. Redox modulating small molecules having antimalarial efficacy. Biochem Pharmacol. 2023 218:115927. PMID: 37992998.