NRH salvage and conversion to NAD+ requires NRH kinase activity by adenosine kinase. Academic Article uri icon

Overview

abstract

  • Dihydronicotinamide riboside (NRH) has been suggested to act as a precursor for the synthesis of NAD+, but the biochemical pathway converting it has been unknown. Here, we show that NRH can be converted into NAD+ via a salvage pathway in which adenosine kinase (ADK, also known as AK) acts as an NRH kinase. Using isotope-labelling approaches, we demonstrate that NRH is fully incorporated into NAD+, with NMNH acting as an intermediate. We further show that AK is enriched in fractions from cell lysates with NRH kinase activity, and that AK can convert NRH into NAD+. In cultured cells and mouse liver, pharmacological or genetic inhibition of AK blocks formation of reduced nicotinamide mononucleotide (NMNH) and inhibits NRH-stimulated NAD+ biosynthesis. Finally, we confirm the presence of endogenous NRH in the liver with metabolomics. Our findings establish NRH as a natural precursor of NAD+ and reveal a new route for NAD+ biosynthesis via an NRH salvage pathway involving AK.

publication date

  • April 21, 2020

Research

keywords

  • Adenosine Kinase
  • NAD
  • Niacinamide

Identity

PubMed Central ID

  • PMC7384296

Scopus Document Identifier

  • 85083766483

Digital Object Identifier (DOI)

  • 10.1007/978-1-4939-1875-1_4

PubMed ID

  • 32694608

Additional Document Info

volume

  • 2

issue

  • 4