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Nicotinamide Adenine Dinucleotide

What is nicotinamide adenine dinucleotide?

Nicotinamide adenine dinucleotide (NAD) is a coenzyme or electron carrier involved in the metabolism of all living cells. We used nicotinamide adenine dinucleotide (NAD⁺ or NADH) supplements in medicine for the treatment or prevention of several types of health diseases such as high blood pressure, cholesterol, depression, and Parkinson’s diseases. NAD⁺ and NADH (NAD⁺ + hydrogen) are the oxidized and reduced forms of nicotinamide adenine dinucleotide molecules. The structure and biological electron transfer or redox reaction of NAD⁺ and NADH is given below the picture,

Nicotinamide adenine dinucleotide NAD and NADH structure, definition, uses in metabolism and oxidized and reduced forms or supplements

The electron transport chain of nicotinamide adenine dinucleotides (NAD⁺ and NADH) is located in the inner membrane of mitochondria. NAD⁺ and NADH are naturally occurring water soluble cofactors in biology. They are involved in several biological redox reactions in all forms of life. The reduced form of nicotinamide adenine dinucleotide stores energy for biological processes. It has power for the production of ATP. During the catabolic reaction, carbohydrates, fats, and proteins can be transferred protons and electrons to NAD⁺.

NAD structure

The chemical formula of nicotinamide adenine dinucleotide is C₂₁H₂₇N₇O₁₄P₂. Generally, the structure of NAD contains two nucleosides joined by a pyrophosphate group.

One nucleoside contains a ribose ring attached with an adenine molecule at the first carbon atom.
Other nucleosides also contain a ribose ring but attaching group is nicotinamide.

In chemistry, NAD is formed by four chemical components,

A nicotinamide
An adenine
Two phosphate sugar (D-ribose)
Two phosphate group

The coenzyme nicotinamide adenine dinucleotide or NAD functions as an acceptor of hydrogen atoms and electrons in the presence of enzyme dehydrogenase. Therefore, it is converted to the reduced form NADH.

Structurally, NAD and NADH are also related to NADP and NADPH. A hydrogen atom of the d-ribose ring of NAD is replaced by a phosphate group to form NADP and NADPH is the reduced form of NADP.

NAD biosynthesis pathway

It is synthesized through three main routes or pathways,

de novo pathway
Preiss-Handler pathway
Salvage pathway

de novo pathway

The production of NAD⁺ in the de novo pathway starts with the essential amino acid L-tryptophan in animals and some bacteria or aspartic acid in plants and some bacteria.

The essential amino acid L-tryptophan or aspartic acid is converted to quinolinic acid (QA) in the first step.
The quinolinic acid formed from L-tryptophan or aspartic acid is further converted to nicotinic acid mononucleotide by transfer of a phosphoribose.
Nicotinic acid adenine dinucleotide (NaAD) is formed in the next step by transferring an adenylate.
In the final step of the formation of nicotinamide adenine dinucleotide, the nicotinic acid in NaAD has converted to nicotinamide (Nam).
In a further step, some NAD⁺ is converted into NADP⁺ by the influence of the enzyme NAD⁺ kinase.

Preiss Handler pathway

Preiss-Handler pathway converts nicotinic acid or vitamin B3 obtained from the diet into NAD⁺ by several types of enzymes.

In the first step, the dietary nicotinic acid is converted to NAMN by the enzyme nicotinic acid phosphoribosyltransferase (NAPRT).
It is then transformed into NAAD by the enzyme NAMN transferase (NMNAT).
In the last step, NAAD is transformed into NAD⁺ by the enzyme NAD⁺ synthase (NADS).

Salvage pathway

In the Salvage pathway, NAM is converted to nicotinamide mononucleotide (NMN) by the rate-limiting enzyme NAMPT. It is then adenylated by the enzyme nicotinamide mononucleotide adenylyl transferase (NMNATs) to form a nicotinamide adenine dinucleotide molecule.

Function of nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide has been studied and researched extensively for many decades and continues to find new roles and functions of NAD. The main function of NAD is oxidative phosphorylation and ATP production in living cells.

DNA repair, gene expression, intracellular calcium signaling, and immunological developments are other functions of NAD. It also involved protein modifications inside the cells. Due to protein modification activity, it acts as a signaling substrate.

What is nicotinamide adenine dinucleotide used for?

Nicotinamide adenine dinucleotide (NAD⁺ and NADH) is an essential coenzyme which involved in a wide number of biological processes in metabolism. NAD⁺ and NADH are controlling mainly biological redox reactions in all forms of life. They are plays a significant role in glycolysis, oxidative phosphorylation, and fermentation reactions.

NAD⁺ is a hydride-accepting coenzyme that is used for oxidation reactions in metabolism. NAD⁺ is used for the production of such enzymes which are involved in DNA damage repair and calcium signaling pathways inside the cells.

NADH is used for improving mental clarity, alertness, concentration, and memory. Recent studies have shown that enhancing NAD⁺ levels can reduce oxidative cell damage in catabolic tissue. Therefore, intracellular NAD⁺ therapy is used to solve age-associated problems or diseases.

The enzymes produced by NAD⁺ and NADH are important in medical chemistry and clinical research. Therefore, they are used in drug design and drug development. These processes are carried out in three ways,

By direct targeting of drugs.
By designing enzyme inhibitors or activators for nicotinamide adenine dinucleotide enzymes.
By controlling the biosynthesis of NAD⁺ and NADH.