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10.1007/s00586-016-4459-7 41 EjtehadifarM.ShamsasenjanK.MovassaghpourA.AkbarzadehlalehP.DehdilaniN.AbbasiP.et al (2015)

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Mechanism of Action and Target Biology NNMT Enzyme and Function: Nicotinamide N-methyltransferase (NNMT) catalyzes the SAM-dependent methylation of nicotinamide: Reaction: Nicotinamide + SAM 1-methylnicotinamide (1-MNA) + S-adenosylhomocysteine (SAH) Expression: Liver, adipose tissue (particularly visceral), smooth muscle, some neurons Regulation: Increased expression in obesity, diabetes, aging, certain cancers Substrates consumed: Nicotinamide (NAD+ precursor) and SAM (methyl donor) 5-Amino-1MQ Inhibition Mechanism: Competitive inhibitor with respect to nicotinamide substrate IC: Submicromolar range for NNMT enzyme Selectivity: Minimal inhibition of other methyltransferases at relevant concentrations Result: Increased intracellular nicotinamide availability for NAD+ salvage pathway Downstream Effects of NNMT Inhibition: 1

Downstream analysis was conducted in R (v.4.4.0) using the Seurat package v.5.1.0 (Hao et al, 2024)