Figure 3.

“NAM drain” concomitantly affects NAD⁺ salvage pathway and methionine cycle. Excessive nicotinamide (NAM) clearance by its nicotinamide N-methyltransferase (NNMT)-mediated methylation excludes NAM from the salvage pathway and consumes methyl units from S-adenosyl methionine (SAM) to generate N1-methylnicotinamide and S-adenosyl homocysteine (SAH). Enzyme S-adenosyl-L-homocysteine hydrolase (SAHase) converts SAH into homocysteine (Hcy). Conditions of high NAD⁺ consumption and liberation of NAM, as well as excessive dietary intake of vitamin B3, promote “NAM drain”-mediated clearance of surplus NAM. This process stalls NAD⁺ synthesis in the salvage pathway, decreases methylation potential of the cell and augments the generation of (Hcy).