NADPHproducing

NADPH-producing refers to the biochemical processes and enzymes that generate NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate. NADPH acts as a key reducing agent in biosynthetic reactions such as fatty acid and cholesterol synthesis, and it provides reducing power to antioxidant systems like glutathione and thioredoxin to maintain redox balance in cells.

The largest and best-characterized source of NADPH is the oxidative phase of the pentose phosphate pathway, where glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase generate NADPH in the cytosol. Additional cytosolic NADPH comes from malic enzyme 1 (ME1) and cytosolic isocitrate dehydrogenase 1 (IDH1). In mitochondria, NADPH is produced by isocitrate dehydrogenase 2 (IDH2) and malic enzymes ME2 and ME3. The mitochondrial nicotinamide nucleotide transhydrogenase (NNT) can generate NADPH by transferring reducing equivalents from NADH to NADP+, driven by the proton gradient. One-carbon metabolism involving MTHFD enzymes also yields NADPH in cytosol and mitochondria.

Biological roles of NADPH production include supporting anabolic growth (lipid, nucleotide, and cofactor synthesis) and protecting cells from oxidative stress. Cells modulate NADPH production in response to energy status, nutrient availability, and redox demands, adjusting flux through PPP and other NADPH-generating routes as needed.

Clinical and research relevance arises from the importance of NADPH in health and disease. Defects in NADPH-producing pathways, such as G6PD deficiency, impair redox defense and can cause hemolysis under oxidative stress. In cancer and metabolic diseases, enhanced NADPH supply supports rapid growth and redox homeostasis, making NADPH metabolism a focus of therapeutic and biotechnological study.