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Nicotinamide Coenzymes

Nicotinamidi coenzymum (NAD+, NADP+)

For medical students2 min readUpdated 2026-10-10

Nicotinamide coenzymes are essential components of enzymes that facilitate oxidation-reduction (redox) reactions. This group includes nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), which act as universal electron and proton acceptors.

Main representativesNicotinamide adenine dinucleotide (NAD+) and Nicotinamide adenine dinucleotide phosphate (NADP+)
Precursor vitaminVitamin PP (niacin), Vitamin B3, nicotinic acid, nicotinamide
Enzyme classOxidoreductases (subclass: dehydrogenases)
Transferred particleHydride ion (1 proton and 2 electrons)

Origin and Role in Enzymes

Nicotinamide coenzymes are synthesized in the body from specific precursor molecules. The primary building block for their formation is vitamin $PP$ (also known as niacin or vitamin $B_3$). Chemically, the precursors are nicotinic acid and nicotinamide.

In biochemical reactions, NAD+ and NADP+ do not function independently. They serve as coenzymes—the non-protein portions of complex enzymes belonging to the oxidoreductase class. More specifically, they are part of the dehydrogenase subclass, which are enzymes that catalyze the removal of hydrogen atoms from a substrate.

Mechanism of Action: Electron and Proton Transfer

The primary task of nicotinamide coenzymes is to participate in substrate oxidation. In this context, the substrate acts as a proton donor (often denoted as $D$ in reaction schemes). The process follows a strict mechanism:

  1. A total of 2 protons ($2H^+$) and 2 electrons ($2e^-$) are removed from the oxidized substrate molecule.
  2. The coenzyme (NAD+ or NADP+) does not take all of these particles. Only 1 proton ($H^+$) and 2 electrons ($2e^-$) attach to it. This combination (one proton plus two electrons) is known as a hydride ion.
  3. The remaining second proton ($H^+$) is not bound to the coenzyme molecule; instead, it is released into the surrounding environment (solution).

This is why the reduced form of the coenzyme is always written with the addition of a free proton: $NADH + H^+$ (or $NADPH + H^+$).

Chemical Reaction and Structural Changes

The attachment of a hydride ion leads to significant structural changes in the active part of the coenzyme—the nicotinamide pyridine ring.

This transition between the oxidized (aromatic, charged) and reduced (non-aromatic, uncharged) states enables coenzymes to transfer reducing equivalents within the cell.

Mnemonic

It is easy to remember the distribution of hydrogen: the substrate gives up the "full set" (2 protons and 2 electrons), but the coenzyme takes a hydride ion (1 proton + 2 electrons) and simply "dumps" the remaining 1 proton into the medium. Hence the notation: NADH + H+.

Frequently asked questions

What is the biochemical difference between the cellular functions of NAD+ and NADP+?

The functions of these coenzymes differ based on the participation of their oxidized and reduced forms in metabolic reactions.

CoenzymeFunction
$NAD^+$ / $NADH$$NAD^+$ participates in substrate oxidation, being reduced to $NADH+H^+$. During glycolysis, the oxidation of glyceraldehyde-3-phosphate generates $NADH+H^+$; under anaerobic conditions, $NADH$ is used to reduce pyruvate to lactate, regenerating $NAD^+$. Ethanol catabolism requires $NAD^+$, increasing $NADH$ levels.
$NADP^+$ / $NADPH$$NADP^+$ is reduced to $NADPH+H^+$ during the oxidative phase of the pentose phosphate pathway. $NADPH$ serves as a hydrogen donor in reduction reactions, including fatty acid and cholesterol synthesis, participates in hydroxylation reactions during xenobiotic detoxification, glutathione reduction, and the production of reactive oxygen species during the respiratory burst.
What are some examples of NAD-dependent dehydrogenases?

Examples of NAD-dependent dehydrogenases include:

  • 3-Phosphoglycerate dehydrogenase — catalyzes the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate, reducing $NAD^+$ to $NADH+H^+$.
  • Glyceraldehyde-3-phosphate dehydrogenase — oxidizes glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, producing $NADH+H^+$.
  • Lactate dehydrogenase — catalyzes the reaction: pyruvate + $NADH+H^+$ ⇄ lactate + $NAD^+$.
  • Alcohol dehydrogenase — an enzyme of ethanol metabolism that requires $NAD^+$ for ethanol oxidation.
In which specific metabolic pathways is NADPH produced?

NADPH is produced through several specific metabolic pathways and reactions:

  • Pentose phosphate pathway — the oxidative phase (reactions catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase).
  • Conversion of malate to pyruvate — malic enzyme-catalyzed decarboxylation of malate.
  • Oxidation of isocitrate — catalyzed by cytosolic isocitrate dehydrogenase.
Which vitamin is the precursor for NAD+ and NADP+?

Their precursor is vitamin PP (niacin, vitamin B3), in the form of nicotinic acid or nicotinamide.

Which enzymes contain nicotinamide coenzymes?

They function as part of oxidoreductases, specifically the dehydrogenase subclass.

How does the structure of NAD+ change upon reduction?

The nicotinamide pyridine ring is reduced: its aromaticity is disrupted, and hydrogen binds at the para-position to the nitrogen atom.

How many protons and electrons does the coenzyme accept from the substrate?

The coenzyme molecule itself accepts 1 proton and 2 electrons (a hydride ion). The second proton removed from the substrate enters the surrounding environment.

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