NADPdependent

NADP-dependent refers to enzymes that catalyze reactions using NADP+ as a cofactor, typically yielding NADPH in the process. These enzymes have specificity for the phosphorylated form of the dinucleotide; some enzymes can utilize either NADP+ or NAD+ and are described as NAD(P)-dependent.

In metabolism, NADPH acts as a reducing equivalent, supporting anabolic biosynthesis and defense against oxidative stress. NADP+-dependent enzymes contribute to the generation of NADPH in pathways such as the oxidative branch of the pentose phosphate pathway, photosynthetic light reactions in plants, and various cytosolic and mitochondrial reactions involved in lipid, nucleotide, and amino acid synthesis.

Prominent examples include glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway; NADP+-dependent isocitrate dehydrogenase (IDH1/IDH2) in cytosol and mitochondria; and malic enzyme (ME), which converts malate to pyruvate with production of NADPH.

Molecular recognition: Many NADP+-dependent enzymes have a Rossmann fold with a binding pocket that recognizes the 2'-phosphate of NADP+. The NADP+/NADPH ratio influences enzyme activity and cellular redox state, helping coordinate metabolic flux with cellular needs.

Physiological relevance: NADP+-dependent NADPH production is essential for redox homeostasis, fatty acid and cholesterol synthesis, and detoxification processes (for example, glutathione and thioredoxin systems). Defects in NADPH-producing enzymes, such as G6PD, can impair antioxidant capacity and contribute to oxidative damage in cells susceptible to oxidative stress.