NAD biosynthesis via nicotinamide riboside salvage pathway

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of nicotinamide adenine dinucleotide (NAD) from the vitamin precursor nicotinamide riboside. [PMID:17482543]

NAD biosynthesis via nicotinamide riboside salvage pathway is a critical metabolic route for generating nicotinamide adenine dinucleotide (NAD+), a vital coenzyme involved in numerous cellular processes, including energy production (via oxidative phosphorylation), DNA repair, and signal transduction. This pathway utilizes nicotinamide riboside (NR), a naturally occurring NAD+ precursor, as its substrate.

The pathway commences with the uptake of NR from the extracellular environment or intracellular sources. NR is then transported into the cytoplasm, where it encounters the enzyme nicotinamide riboside kinase (NRK). NRK catalyzes the phosphorylation of NR to nicotinamide mononucleotide (NMN), using ATP as a phosphate donor.

NMN serves as the substrate for the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT), which catalyzes the final step in NAD+ biosynthesis from NR. NMNAT utilizes ATP to adenylylate NMN, yielding NAD+. This reaction occurs predominantly in the nucleus, where NAD+ is required for various nuclear functions.

The nicotinamide riboside salvage pathway is highly efficient and provides a significant contribution to the cellular NAD+ pool. Notably, NR is readily absorbed from the diet and can be synthesized in various tissues, contributing to the pathway's importance in maintaining cellular NAD+ homeostasis.

In addition to its role in NAD+ biosynthesis, the nicotinamide riboside salvage pathway also plays a crucial role in regulating cellular NAD+ levels. The pathway is tightly regulated by the availability of NR, the activity of NRK and NMNAT, and the cellular NAD+ demand.

Overall, the nicotinamide riboside salvage pathway is a fundamental metabolic process that ensures adequate NAD+ levels for various cellular functions. This pathway is essential for maintaining cellular health and has gained significant attention for its potential therapeutic implications in various diseases, including aging and neurodegenerative disorders.'
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Proteins (12)

Compounds (37)