NNMT Recombinant Rabbit mAb (S-3470-58)

Nicotinamide N-methyltransferase (NNMT) is a cytosolic metabolic enzyme encoded by a gene located on chromosome 11q23.2. Its core biochemical function is the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide (NAM), generating 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). This reaction positions NNMT as a pivotal nexus linking methylation metabolism, NAD⁺ synthesis, and epigenetic regulation. NNMT's sustained consumption of the SAM substrate not only limits methyl donor availability for DNA methyltransferases and histone methyltransferases—leading to loss of repressive histone marks such as H3K27me3 and global DNA hypomethylation—but also depletes the NAD⁺ precursor nicotinamide, thereby impairing mitochondrial respiration and the activity of deacetylases such as SIRT1. This accelerates mitochondrial dysfunction and neuronal apoptosis in neurodegenerative diseases, while within the tumor microenvironment, it drives the activation and differentiation of cancer-associated fibroblasts (CAFs) and recruits myeloid-derived suppressor cells (MDSCs) via the complement cascade to establish an immunosuppressive niche. Research has confirmed that NNMT is specifically upregulated by the glucocorticoid receptor signaling axis in glioblastoma, where its product 1-MNA is enriched approximately 7-fold in tumor tissue compared to adjacent normal tissue—a disparity now exploited for [¹¹C] nicotinamide PET imaging strategies. In hypertrophic scars, NNMT-mediated NAD⁺ and SAM depletion drives macrophage-to-myofibroblast transdifferentiation (MMT) through accumulation of H3K27ac and loss of H3K27me3; NNMT knockdown disrupts the interaction between the transcription factor Prrx1 and super-enhancers, significantly reducing scar volume.