NADHNADPH

NADH (nicotinamide adenine dinucleotide, reduced) and NADPH (nicotinamide adenine dinucleotide phosphate, reduced) are two phosphorylated derivatives of the dinucleotide NAD+ and NADP+. They function as essential redox cofactors in cells, carrying electrons during many metabolic reactions. They differ in the phosphate group on the ribose of the nicotinamide mononucleotide moiety, which influences enzyme specificity and the cellular compartment where each cofactor primarily operates.

NADH primarily participates in catabolic energy production. In mitochondria it transfers electrons to the electron transport chain, contributing to ATP synthesis via oxidative phosphorylation. NADH is generated mainly in glycolysis, the pyruvate dehydrogenase complex, and the tricarboxylic acid cycle. It does not accumulate to drive biosynthesis; instead it is shuttled across membranes by malate–aspartate or glycerol phosphate shuttles.

NADPH provides reducing power for anabolic reactions and defense against oxidative stress. It is produced mainly through the pentose phosphate pathway in the cytosol, and by enzymes such as malic enzyme and cytosolic isocitrate dehydrogenase. NADPH supplies electrons for fatty acid, cholesterol, and nucleotide synthesis, and sustains the glutathione and thioredoxin systems that maintain redox balance and detoxification.

Enzyme specificity depends on the cofactor: many dehydrogenases use NAD+, whereas separate enzymes use NADP+. The cellular NAD+/NADH ratio is kept high to favor oxidation and energy production, while the NADP+/NADPH ratio is maintained to support biosynthesis and antioxidant capacity. Dysfunction in NADH or NADPH production or recycling is linked to metabolic disorders and impaired immune function.