NAD biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of nicotinamide adenine dinucleotide, a coenzyme present in most living cells and derived from the B vitamin nicotinic acid; biosynthesis may be of either the oxidized form, NAD, or the reduced form, NADH. [GOC:jl, ISBN:0618254153]

The NAD biosynthetic process is a crucial metabolic pathway responsible for the production of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme essential for numerous cellular processes. This process can be divided into two primary pathways: de novo synthesis and salvage pathways.

**De novo synthesis** involves the formation of NAD+ from simple precursors like tryptophan or aspartate.

* **Tryptophan pathway:** In this pathway, tryptophan is converted to quinolinate, which then undergoes several enzymatic steps to form nicotinate mononucleotide (NaMN). NaMN is further phosphorylated to nicotinate adenine dinucleotide (NaAD) and then converted to NAD+.
* **Aspartate pathway:** This pathway utilizes aspartate to synthesize quinolinate, following a similar route to the tryptophan pathway for the subsequent steps.

**Salvage pathways** utilize pre-existing components like nicotinamide, nicotinic acid, or nicotinamide riboside to synthesize NAD+.

* **Preiss-Handler pathway:** This pathway utilizes nicotinamide as a precursor and involves a series of enzymatic steps catalyzed by nicotinamide phosphoribosyltransferase (NAMPT) to convert it to nicotinamide mononucleotide (NMN). NMN is then phosphorylated to NAD+.
* **Nicotinic acid pathway:** This pathway utilizes nicotinic acid as a precursor and involves its conversion to nicotinate mononucleotide (NaMN) by nicotinate phosphoribosyltransferase (NAPRT). NaMN is then processed similarly to the de novo pathway.
* **Nicotinamide riboside pathway:** This pathway uses nicotinamide riboside as a precursor, directly converting it to NMN by nicotinamide riboside kinase (NRK). NMN is then further processed to NAD+ as described above.

The NAD biosynthetic process is tightly regulated to ensure adequate NAD+ levels, as it is crucial for various essential functions:

* **Redox reactions:** NAD+ acts as an electron carrier, participating in numerous redox reactions, such as those involved in cellular respiration and oxidative phosphorylation.
* **DNA repair:** NAD+ is essential for DNA repair mechanisms, particularly the base excision repair pathway.
* **Signaling pathways:** NAD+ serves as a substrate for various signaling enzymes, including sirtuins, which play critical roles in regulating gene expression, aging, and stress response.
* **Calcium signaling:** NAD+ is involved in the regulation of calcium signaling pathways, essential for various cellular processes.

Deficiencies in NAD+ synthesis can lead to various health issues, including neurological disorders, metabolic diseases, and impaired immune function. Therefore, maintaining proper NAD+ levels through dietary intake or supplementation is crucial for overall health and well-being.'
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Proteins (3)

Compounds (12)