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In parallel with MTXs most well-known targets, several NAD+-dependent enzymes were inhibited by the antifolate in vitro : 2-oxoglutarate, isocitrate, malate, pyruvate, succinate, 6-phosphogluconate and glucose-6-phosphate dehydrogenases, glutamate-cysteine ligase, glutathione reductase, and glutathione peroxidase (29)

Enzymes in blue are involved in NAD + synthesis, while enzymes in red are NAD + -consuming

and Feldman, E.L

108 KuehneltD.JuresaD.KienzlN.FrancesconiK

Quantification of glutathione concentration Assays were performed on brain tissue and plasma samples using the GSSG/GSH Quantification Kit (Dojindo, Kumamoto, Japan )