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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: Biochem Pharmacol. 2019 Feb 10;163:481–492. doi: 10.1016/j.bcp.2019.02.008

Figure 6.

Figure 6.

Schematic illustration of pathways regulated by NNMT and proposed working model of mechanisms of action of NNMT inhibition as it relates to muSC activation and metabolic state in aged muscle tissue. Maintenance of flux through the NAD salvage pathway by NNMTi is indicated by gradient blue/red arrow; (i) increase flux of NAD+, activated SIRT-1, and oxidative metabolism that support quiescent muSCs are indicated by red arrows; (ii) increased NADH (i.e., increased NAD+ utilization in glycolysis), enhanced glycolysis, and reduced SIRT-1 mediated histone deacetylation that support muSC activation and differentiation are indicated by blue arrows. Pathway abbreviations include AOx1 (aldehyde oxidase), NA (nicotinamide), MNA (1-methylnicotinmaide), NAMPT (nicotinamide phosphoribosyltransferase), NMN (nicotinamide mononucleoside), NMNAT (nicotinamide adenylyltransferase), NNMT (nicotinamide N-methyltransferase), NR (nicotinamide riboside), NRK (nicotinamide riboside kinase), PNP1 (purine nucleoside phosphorylase), PYR-2/4 (1-methyl-2/4-pyridone-5-carboxamide), SAH (S-adenosyl-L-homocysteine), SAM (S-adenosylmethionine), MTases (methyl transferases), SIRT1 (NAD-dependent deacetylase sirtuin 1), NAD+/NADH (oxidized Nicotinamide adenine dinucleotide/reduced form of NAD+), OXPHOS (oxidative phosphorylation), Histone*protein-Ac/DeAc (Acetylated/deacetylated histones).