NadpEdit

Nicotinamide adenine dinucleotide phosphate, commonly abbreviated NADP, is a versatile coenzyme found in all living cells. It exists in two interconvertible forms: the oxidized NADP+ and the reduced NADPH. In its oxidized state, NADP+ accepts electrons to become NADPH, which then serves as a major hydride donor in reductive biosynthesis and in defense against oxidative stress. The balance between NADP+ and NADPH is tightly regulated and is distinct from the closely related NAD+/NADH pair that primarily participates in energy production.

NADP and NADPH play central roles across diverse biological processes, spanning cellular metabolism, biosynthesis, detoxification, and interactions with photosynthesis in plants. The molecule’s functionality is defined not only by its redox state but also by its cellular localization, with separate cytosolic and organellar pools contributing to distinct metabolic tasks. The following sections outline the structure, generation, roles, and broader significance of NADP and NADPH in biology.

Biochemistry and redox pair NADP+/NADPH

NADP+ is a nucleotide cofactor that carries an adenine dinucleotide backbone bearing an additional phosphate group, which differentiates it from NAD+. This extra phosphate on the 2′-position of the adenosine ribose directs NADP/NADPH to a subset of enzymes and cellular pathways that are distinct from those primarily using NAD+/NADH. See also NADP+ and NADPH for detailed discussions of their chemistry and biological functions.

NADPH acts predominantly as a reducing agent. It provides high-energy electrons for anabolic (biosynthetic) reactions, such as fatty acid synthesis, cholesterol synthesis, and nucleotide synthesis. In these processes, NADPH supplies the reducing power required to convert precursor molecules into complex biomolecules. By contrast, NADP+ is the oxidized form that accepts electrons during catabolic reactions and replenishes the redox balance of the cell when electrons are supplied by photosynthetic or respiratory activities. See Fatty acid synthesis, Cholesterol biosynthesis, and Nucleotide synthesis for examples of NADPH-dependent biosynthetic pathways.

In addition to supporting anabolism, NADPH is essential for maintaining cellular redox homeostasis. It supplies reducing equivalents to antioxidant systems such as Glutathione and Thioredoxin systems through enzymes like Glutathione reductase and Thioredoxin reductase. This helps protect cells from damage caused by reactive oxygen species. In immune defense, NADPH is a substrate for the NADPH oxidase complex, which generates reactive oxygen species used by phagocytes in microbial killing. See Glutathione and NADPH oxidase for related concepts.

NADPH is also central to photosynthesis in plants and algae. In chloroplasts, light reactions reduce NADP+ to NADPH via ferredoxin-NADP+ reductase (FNR). The resulting NADPH then fuels the Calvin cycle, enabling carbon fixation and carbohydrate production. See Photosynthesis, Ferredoxin-NADP+ reductase, and Calvin cycle for broader context.

Generation and regulation of NADPH pools

Cells generate NADPH primarily through three major processes:

The pentose phosphate pathway (PPP), particularly its oxidative phase, which converts glucose-6-phosphate into ribulose-5-phosphate while reducing NADP+ to NADPH. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of this oxidative phase and a key regulatory node. See Pentose phosphate pathway and Glucose-6-phosphate dehydrogenase.
NADP+-dependent isocitrate dehydrogenase (IDH) enzymes in some tissues (IDH1 in cytosol and IDH2 in mitochondria) that generate NADPH during citric acid cycle flux.
NADP+-dependent malic enzymes that convert malate to pyruvate while producing NADPH, contributing to redox balance and biosynthetic capacity.

The cellular NADPH pool is compartmentalized, with distinct pools in the cytosol, mitochondria, and plastids in plants. Regulation of the NADPH/NADP+ ratio integrates signals from metabolism, oxidative stress, and growth demands, allowing cells to adapt to changing environmental and physiological conditions. See NADP+ and NADPH for more on redox biology; see Pentose phosphate pathway for pathway-specific details.

Roles in metabolism

NADPH provides reducing equivalents for a wide range of biosynthetic processes, including:

Fatty acid synthesis in the cytosol
Cholesterol and other isoprenoid biosynthesis
Nucleotide and nucleic acid precursor formation

NADPH also sustains antioxidant defenses and detoxification mechanisms. Key examples include:

Glutathione reduction via Glutathione reductase, enabling glutathione to detoxify peroxides
Thioredoxin system maintenance via Thioredoxin reductase

In addition, NADPH participates in cellular defense and signaling pathways, and it is a substrate for certain reductive enzymes involved in drug metabolism and xenobiotic detoxification (for example, some activities of the Cytochrome P450 system rely indirectly on the NADPH supply). See Glutathione and Cytochrome P450.

Plant biology and photosynthesis

In plant cells and algae, NADPH produced in the light reactions provides the reducing power for carbon assimilation in the chloroplasts. The light-driven transfer of electrons through photosystem I culminates in the reduction of NADP+ to NADPH by FNR, which then feeds the Calvin cycle to fix carbon into triose phosphates and ultimately synthesize sugars. See Photosynthesis, Photosystem I, and Calvin cycle.

Health, disease, and population relevance

Variations in NADPH production and availability can influence susceptibility to oxidative stress and metabolic disorders. Notable considerations include:

G6PD deficiency reduces the oxidative capacity of the PPP’s initial step, which can compromise NADPH production in red blood cells and elevate risk for oxidative hemolysis under stressors such as certain infections, drugs, or foods. See G6PD deficiency.
Adequate NADPH is essential for maintaining redox balance in many tissues; insufficient NADPH can contribute to cellular stress, while excess NADPH activity has been discussed in relation to certain cancer cell metabolism and drug resistance under some conditions. See Redox and Cancer metabolism for broader discussions.
In the immune system, NADPH-dependent production of reactive oxygen species via NADPH oxidase is a critical antimicrobial mechanism, illustrating how NADPH supports host defense.

History and terminology

NADP and its reduced form NADPH were identified in the mid-20th century as researchers uncovered cofactors needed for anabolic biosynthesis and for protecting cells against oxidative damage. The NADP/NADPH system is now understood as a fundamental component of cellular metabolism, linking energy, redox state, and the synthesis of essential biomolecules.