NADPHgenerating

NADPH-generating refers to biochemical processes and enzymes that produce nicotinamide adenine dinucleotide phosphate in its reduced form, NADPH. NADPH serves as a primary reducing agent in anabolic reactions and in cellular defense against oxidative stress, providing electrons for biosynthetic pathways such as fatty acid and nucleotide synthesis, as well as for antioxidant systems that restore redox balance.

The main cellular sources of NADPH include the oxidative phase of the pentose phosphate pathway, driven by glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase. Cytosolic and mitochondrial NADPH can also arise from isocitrate dehydrogenases (IDH1 in the cytosol and IDH2 in mitochondria) and from malic enzymes (ME1 in the cytosol and ME2/ME3 in organelles) that convert malate to pyruvate or related intermediates while reducing NADP+ to NADPH. Additionally, folate cycle enzymes such as methylenetetrahydrofolate dehydrogenase (MTHFD1 and related isoforms) generate NADPH as part of one-carbon metabolism. These sources collectively support NADPH production in different cellular compartments and metabolic states.

Regulation of NADPH-generating pathways varies by tissue and condition. The pentose phosphate pathway often upregulates in response to oxidative stress or high anabolic demand to supply NADPH for detoxification and biosynthesis. In many cancers, enhanced NADPH production supports rapid growth and redox balance, making these pathways potential therapeutic targets. Beyond biosynthesis, NADPH is essential for maintaining the redox state via enzymes such as glutathione reductase and thioredoxin reductase, underscoring the central role of NADPH-generating systems in cellular metabolism and defense.