Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells

• DOI: 10.1016/j.jbc.2022.102615
• Publication Date: 2022-10-18T07:56:59Z
• Authors: Andrey Kropotov; Veronika Kulikova; Ljudmila Solovjeva; Alexander Yakimov; Kirill Nerinovski; Maria Svetlova; Julia Sudnitsyna; Alena Plusnina; Maria Antipova; Mikhail Khodorkov...; Marie E. Migaud; Stepan Gambaryan; Mathias Ziegler; Andrey Nikiforov
• Keywords: Riboside; Purine metabolism; Ribose

Nicotinamide riboside (NR) is an effective precursor of nicotinamide adenine dinucleotide (NAD) in human and animal cells. NR supplementation can increase the level NAD various tissues thereby improve physiological functions that are weakened or lost experimental models aging pathologies. However, there also reports questioning efficacy supplementation. Indeed, mechanisms its utilization by cells not fully understood. Herein, we investigated role purine nucleoside phosphorylase (PNP) metabolism mammalian Using both PNP overexpression genetic knockout, show after being imported into members equilibrative transporter family, predominantly metabolized PNP, resulting (Nam) accumulation. Intracellular cleavage to Nam prevented potent inhibitor Immucillin H types In turn, suppression activity potentiates synthesis from NR. Combining pharmacological inhibition with mice, demonstrate strongly diminished, maintaining high levels blood, kidney, liver. Moreover, stimulates mononucleotide NAD+ vivo, particular, kidney. Thus, establish as a major regulator mammals provide evidence health benefits could be greatly enhanced concomitant downregulation activity.