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Nicotinamide adenine dinucleotide

life science Maturity 5-7 Next article →

Nicotinamide adenine dinucleotide, or NAD, is a vital coenzyme found in every living cell. A coenzyme is a small molecule that helps enzymes perform their biological functions. NAD is classified as a dinucleotide because its structure consists of two nucleotides joined by phosphate groups. One nucleotide contains the nucleobase adenine, while the other contains nicotinamide. This molecule is essential for metabolism, which is the set of chemical processes that keep life running.

Rossman fold
Rossman fold

The primary function of NAD is to participate in redox reactions. These are chemical processes involving the transfer of electrons between molecules. In these reactions, NAD acts as an oxidizing agent by accepting electrons from other molecules. When it accepts these electrons, it becomes the reduced form known as NADH. NADH can then act as a reducing agent by donating electrons to a different molecule. This process involves a hydride ion, which consists of two electrons and one proton. The hydride is transferred to the nicotinamide ring, while the proton is released into the solution.

NAD oxidation reduction
NAD oxidation reduction

This electron transfer is a reversible cycle. Because the reaction is easily reversed, the coenzyme can cycle between NAD and NADH without being consumed. This continuous cycling allows the cell to manage energy efficiently. NAD is also used in posttranslational modifications. This means it helps enzymes add or remove chemical groups from proteins. Because these functions are so critical, enzymes that manage NAD are major targets for drug discovery.

Catabolism schematic
Catabolism schematic

Cells produce NAD through two distinct pathways: de novo synthesis and the salvage pathway. De novo synthesis means building the molecule from scratch using simple building blocks. In animals, this process often starts with the amino acid tryptophan. In some bacteria and plants, it begins with the amino acid aspartic acid. These pathways eventually produce quinolinic acid, which is then converted into nicotinic acid adenine dinucleotide (NaAD) before becoming final NAD.

NAD metabolism
NAD metabolism

The salvage pathway is an alternative method that recycles preformed components. It uses precursors like nicotinic acid, nicotinamide, or nicotinamide riboside. These precursors are often obtained through the diet as vitamin B3, also known as niacin. In mammals, the salvage pathway is the primary source of NAD. This recycling is essential because a lack of niacin in the diet can lead to a deficiency disease called pellagra.

NA, N and NR
NA, N and NR

There is also a related molecule called NADP, or nicotinamide adenine dinucleotide phosphate. NADP is similar to NAD but includes an extra phosphate group. While NAD is mainly used in energy-releasing reactions, NADP is used in anabolic metabolism. Anabolic metabolism refers to processes that build complex molecules, such as lipids and nucleic acids. NADP exists in two forms: the oxidized NADP+ and the reduced NADPH.

NAD metabolism
NAD metabolism

Scientists use unique physical properties to study these molecules in the lab. Both NAD and NADH absorb ultraviolet light due to the presence of adenine. However, they absorb light at different wavelengths. NAD peaks at 259 nanometers, while NADH has a second peak at 339 nanometers. This difference allows researchers to use a spectrophotometer to measure how much one form converts to the other. Additionally, NADH exhibits fluorescence, meaning it glows blue or violet when excited by light.

NADNADH
NADNADH

The balance between these forms is known as the NAD/NADH ratio. This ratio is a key indicator of the redox state of a cell. The redox state reflects both the metabolic activity and the overall health of the cell. In healthy mammalian cytoplasm, the ratio of free NAD to NADH is typically around 700:1. This high ratio is favorable for oxidative reactions. In contrast, the ratio of total NAD to NADH in mammals is much lower, usually between 3 and 10.

NADNADH
NADNADH
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🖼️ Images & Media (9)
File:NAD oxidation reduction.svg
NAD oxidation reduction.svg
File:NADNADH.svg
NADNADH.svg
File:NAD metabolism.svg
NAD metabolism.svg
File:NA, N and NR.svg
NA, N and NR.svg
File:Rossman fold.png
Rossman fold.png
File:NAD+ phys alt.svg
NAD+ phys alt.svg
File:Catabolism schematic.svg
Catabolism schematic.svg
File:Cyclic ADP ribose.svg
Cyclic ADP ribose.svg
File:ArthurHarden.jpg
ArthurHarden.jpg
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