ArticleThe Journal of biological chemistry2015
Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial.GeroScience · 2026Article
- Autophagic therapeutic targeting for Doxorubicin-induced cardiomyopathy.Molecular biology reports · 2026Review
- Immune-proteo-metabolomic changes link to Aβ and tau pathology in Alzheimer disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Nicotinic acid riboside maintains NADCell metabolism · 2025Article
- Nicotinamide riboside and nicotinamide mononucleotide facilitate NADScience advances · 2025Article
- Regulation of and challenges in targeting NADNature reviews. Molecular cell biology · 2024Review
- Ototoxic Effect of Nicotinamide Riboside.Bulletin of experimental biology and medicine · 2024Article
- Preventing loss of sirt1 lowers mitochondrial oxidative stress and preserves C2C12 myotube diameter in an in vitro model of cancer cachexia.Physiological reports · 2024Article
- A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.The Journal of clinical investigation · 2024Article
- Nicotinamide Riboside, a Promising Vitamin BMolecules (Basel, Switzerland) · 2023Review
- What is really known about the effects of nicotinamide riboside supplementation in humans.Science advances · 2023Review
- The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.International journal of molecular sciences · 2023Review
- Article
- Emerging Role of Nicotinamide Riboside in Health and Diseases.Nutrients · 2022Review
- Balancing NADCellular and molecular life sciences : CMLS · 2022Review
- NADMetabolites · 2022Review
- Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NADNutrients · 2022Article
- Fueling genome maintenance: On the versatile roles of NADThe Journal of biological chemistry · 2022Review
- Article
- Nicotinic Acid Riboside Regulates Nrf-2/P62-Related Oxidative Stress and Autophagy to Attenuate Doxorubicin-Induced Cardiomyocyte Injury.BioMed research international · 2022Review
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.