Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans

Summary

Seminal paper identifying nicotinamide riboside (NR) as a bona fide NAD+ precursor vitamin and defining the nicotinamide riboside kinase (NRK1/NRK2) pathway that converts it to NMN and then NAD+ independently of the classical Preiss-Handler route. Using yeast genetics, Bieganowski and Brenner screened for suppressors of a qns1 NAD+ auxotroph and recovered NR as a salvageable precursor. They cloned the NRK1 gene, then identified the human orthologs NRK1 (NMRK1) and NRK2 (NMRK2), showing both possessed kinase activity on NR. This established a third route to NAD+ in mammals, alongside the de novo tryptophan pathway and the Preiss-Handler route from nicotinic acid. The discovery directly enabled the development of NR as an oral supplement — because the NRK pathway is present in humans, dietary NR could be converted to NAD+ in tissues without requiring deamidation. Every subsequent NR clinical trial traces to this mechanistic foundation.

For background on the compound studied here, see our NR precursor reference.

Frequently asked questions

What did Bieganowski et al. (2004) find about NR?

NR is a distinct NAD+ precursor in humans, converted via the conserved NRK1/NRK2 kinases — a route independent of the Preiss-Handler pathway. Source: Bieganowski P, Brenner C "Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans." Cell, 2004.

What kind of study is Bieganowski 2004?

It is a mechanism study on NR published in Cell in 2004. Seminal paper identifying nicotinamide riboside (NR) as a bona fide NAD+ precursor vitamin and defining the nicotinamide riboside kinase (NRK1/NRK2) pathway that converts it to NMN and then NAD+ independently of the classical Preiss-Handler route. Using yeast genetics, Bieganowski and Brenner screened for suppressors of a qns1 NAD+ auxotroph and recovered NR as a salvageable precursor. They cloned the NRK1 gene, then identified the human orthologs NRK1 (NMRK1) and NRK2 (NMRK2), showing both possessed kinase activity on NR. This established a third route to NAD+ in mammals, alongside the de novo tryptophan pathway and the Preiss-Handler route from nicotinic acid. The discovery directly enabled the development of NR as an oral supplement — because the NRK pathway is present in humans, dietary NR could be converted to NAD+ in tissues without requiring deamidation. Every subsequent NR clinical trial traces to this mechanistic foundation.

Where can I read the full Bieganowski 2004 paper?

The primary source is available on PubMed (PMID 15137942) and via DOI 10.1016/s0092-8674(04)00416-7.

Access the full paper

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