Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.
Level 5 - mechanism / opinion, no new human data
Bench and animal research (in vitro muscle cell models and knockout mice)
PubMed 28752046 · doi:10.1016/j.molmet.2017.05.011
What was done
The authors investigated how skeletal muscle cells synthesize NAD+ from nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). They used expression profiling of NAD+ biosynthetic pathways, single and double nicotinamide riboside kinase 1 and 2 (NRK1/2) knockout mouse models, and pharmacological inhibition of NAMPT to evaluate precursor utilization in muscle cells and myotubes.
What was found
The abstract reports qualitative directions without numerical data. NAMPT inhibition depleted muscle NAD+ pools, which was rescued by NR and NMN in an NRK1/2-dependent manner. Nrk2 knockout mice developed normally with subtle alterations in their NAD+ metabolome and gene expression. Experiments in single and double NRK1/2 knockout myotubes showed functional redundancy for NR metabolism and revealed that NMN supplementation also depends on NRK activity to elevate NAD+.
Why it matters
This study delineates the salvage pathways of NAD+ in skeletal muscle, demonstrating that both NR and NMN require the redundant NRK1/NRK2 pathway to support intracellular NAD+ synthesis.
Limits
No quantitative values, effect sizes, or sample sizes are provided in the abstract. The study relies entirely on preclinical rodent and cell culture models, which may not directly reflect human muscle biology or oral precursor pharmacokinetics.
Cited by
- supports Nicotinamide riboside (NR) is a molecule that lacks a phosphate group compared to NMN and must first be phosphorylated into NMN before being synthesized into NAD.