Biological Redox

3 min read Updated Apr 18, 2026

Oxidized and reduced forms of NAD showing electron and hydride transfer in the ring of nicotinamide — NAD+/NADH redox. NAD+ accepts a hydride (2 electrons + 1 proton) to become NADH. The process is reversible and handles most of the cell's oxidative electron transfers. *Credit: Wikimedia Commons, CC BY-SA*

Oxidation is loss of electrons; reduction is gain. Metabolism is a giant redox system that gradually strips electrons from fuel and hands them to oxygen. The intermediate carriers are NAD+, FAD, and NADP+.

NAD+ and FAD

NAD+ (nicotinamide adenine dinucleotide, from niacin/B3): accepts 2 electrons and 1 proton as a hydride, becoming NADH. Central to catabolism. Each NADH yields ~2.5 ATP at the ETC.
FAD (flavin adenine dinucleotide, from riboflavin/B2): accepts 2 electrons and 2 protons, becoming FADH2. Used by enzymes that need to handle oxidations of less chemically reactive bonds (e.g., alkenes in beta-oxidation, succinate → fumarate in TCA). Each FADH2 yields ~1.5 ATP.

NADPH

NADPH is NAD+ with an extra phosphate on the ribose. Same redox chemistry, but kept in a separate pool for biosynthesis:

NADH/NAD+: high-NADH state means “catabolism is running, feed the ETC.”
NADPH/NADP+: high-NADPH state means “reductive biosynthesis can run” and “antioxidant defense is ready.”

The separation lets the cell run catabolism (which raises NADH) and anabolism (which needs NADPH) in parallel without interfering with each other.

Sources of NADPH

Pentose phosphate pathway (PPP): the main source. Important in liver (fatty acid synthesis) and red blood cells (antioxidant defense).
Malic enzyme: part of the citrate shuttle during fatty acid synthesis.
Isocitrate dehydrogenase: some cytoplasmic IDH isoforms generate NADPH.

Reduction Potential

Each redox pair has a standard reduction potential (E°’). More negative E°’ means the pair donates electrons more strongly. NADH (E°’ = -0.32 V) donates to O2 (E°’ = +0.82 V), falling a total of ~1.14 V. That voltage drop through the ETC is converted to the proton motive force.

Why do cells keep NADH and NADPH as separate pools?

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NADH and NADPH have the same redox chemistry but different metabolic roles. NADH feeds the ETC for ATP production (catabolism). NADPH provides reducing power for biosynthesis (fatty acid synthesis, cholesterol synthesis) and antioxidant defense (regeneration of reduced glutathione). Separating the pools lets the cell manage catabolic energy production and anabolic/reductive needs independently.

What vitamin is the precursor for NAD+, and what condition results from severe deficiency?

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Niacin (vitamin B3) is the precursor for both NAD+ and NADP+. Severe deficiency causes pellagra, characterized by the 3 D's: dermatitis (sun-exposed skin), diarrhea, dementia. Pellagra is rare in developed countries but still occurs in settings of chronic alcoholism or malabsorption.

Why does NADH yield more ATP than FADH2 via the ETC?

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NADH has a more negative reduction potential than FADH2 and enters the ETC at Complex I (which pumps protons). FADH2 enters at Complex II (which does NOT pump protons). More protons pumped per NADH means more ATP. Approximate yields: 2.5 ATP per NADH, 1.5 ATP per FADH2.