NRH salvage and conversion to NAD+ requires NRH kinase activity by adenosine kinase.

Nature Metabolism
Yue YangAnthony A Sauve

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.

References

Jun 23, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria Thereza P BarbosaEduardo Nunes Chini
Jan 1, 2008·The Journal of Pharmacology and Experimental Therapeutics·Anthony A Sauve
Apr 5, 2011·Cell Metabolism·Péter BaiJohan Auwerx
Dec 22, 1956·Journal of the American Medical Association·R M WILDER
Apr 9, 2014·EMBO Molecular Medicine·Nahid A KhanAnu Suomalainen
Oct 14, 2014·Methods in Molecular Biology·Wei Li, Anthony A Sauve
Sep 26, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Karim GarianiJohan Auwerx
Oct 13, 2015·Cell Reports·Wenjing XuNancy C Andrews
Oct 21, 2016·Biochimica Et Biophysica Acta·Yue Yang, Anthony A Sauve
Oct 11, 2016·Nature Communications·Samuel A J TrammellCharles Brenner
Aug 9, 2017·The EMBO Journal·Elena Katsyuba, Johan Auwerx
Dec 7, 2017·Nature·Vincenzo SorrentinoJohan Auwerx
Feb 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yujun HouVilhelm A Bohr
Apr 6, 2019·The Journal of Biological Chemistry·Yue YangAnthony A Sauve
May 28, 2019·Nature Metabolism·Alessia GrozioShin-Ichiro Imai
Dec 11, 2019·Cancer Cell·Detlev Boison, Gennady G Yegutkin

❮ Previous
Next ❯

Citations

Jul 23, 2020·Nature Metabolism·Mathias Ziegler, Andrey A Nikiforov
Oct 14, 2020·Biochemistry. Biokhimii︠a︡·V A Kulikova, A A Nikiforov
Dec 20, 2020·Biochemical Pharmacology·Gennady G Yegutkin
Feb 13, 2021·International Journal of Molecular Sciences·Andrey KropotovAndrey Nikiforov
Dec 24, 2020·Nature Reviews. Molecular Cell Biology·Anthony J CovarrubiasEric Verdin
Apr 17, 2021·ACS Pharmacology & Translational Science·Amir E WahbaDetlev Boison
May 28, 2021·EMBO Molecular Medicine·Rubén Zapata-PérezRiekelt H Houtkooper
May 2, 2021·The Journal of Physiology·Morten DallJonas T Treebak
Jun 3, 2021·Nutrients·Moustafa S GhanemAlessio Nencioni
Jun 8, 2021·Frontiers in Molecular Biosciences·Benjamin GrothSu-Ju Lin
Jul 25, 2021·Mechanisms of Ageing and Development·Catherine Li, Lindsay E Wu

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
acetylation
PCR

Software Mentioned

GraphPad Prism
GraphPad
MaxQuant
Protparam EXPASY
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.