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Panel A shows a graph of RBC CAT concentration (U/ml) observed in mice fed 1, 3 and 10 dosage of Protandim-I dietary supplement for 23 days

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

Best evaluated in the context of broader skin health and any underlying nutritional or hormonal contributors

Vitamin D insufficiency does not affect bone mineral density response to raloxifene

Cancer Cell 2005