Evidence of metabolic competition between methionine and glutathione biosynthetic pathways

Cysteine, the first organic sulphur-containing metabolite, serves as a precursor for the synthesis of glutathione and methionine, two metabolites that are central to plant growth and survival. Glutathione plays a crucial role in the defence against a diverse environmental stresses due to its antioxidant function, while methionine is a protein constituent, and through its first metabolite, S-adenosylmethionine, regulates essential processes required for plant growth. To reveal the relations between glutathione and methionine, we used tobacco plants overexpressing the regulatory enzyme of methionine biosynthesis pathway, cystathionine γ-synthase (FA plants). FA plants were significantly more sensitive to oxidative stress than wild-type (WT) plants. Measuring the levels of glutathione in WT plants exposed to oxidative stress (6 h of 150 mM H₂O₂) shows that its level significantly increased, while the level of methionine significantly decreased, compared to untreated plants. Such significant differences were not observed in FA plants. Feeding and metabolic profiling analyses indicated the existence of metabolic competition between the biosynthesis pathways of methionine and glutathione on their common precursor, cysteine, and that this competition is more crucial under oxidative conditions. Immunoblot and transcript analyses had shown that the protein expression level of CGS was significantly reduced, unlike its transcript, when the level of glutathione increased in plants. Further studies have shown that glutathione covalently binds CGS and then reduces its stability. This reduction in CGS and thus in the flux towards methionine and its associated metabolites leave more cysteine that required for the synthesis of glutathione during oxidative stress.