NNMT Protein (Nicotinamide N-methyltransferase) is an enzyme that catalyzes the N-methylation of nicotinamide and other pyridine compounds. It plays a crucial role in NAD+ metabolism, one-carbon metabolism, and has been implicated in neurodegeneration, cancer, and metabolic disorders.
| Attribute |
Value |
| Protein Name |
Nicotinamide N-methyltransferase (NNMT) |
| Gene |
NNMT |
| UniProt ID |
P40261 |
| Molecular Weight |
~30 kDa |
| Subcellular Localization |
Cytoplasm |
| Protein Family |
N-methyltransferase family |
| Associated Diseases |
Parkinson's disease, Alzheimer's disease, cancer |
NNMT is a monomeric enzyme consisting of:
- N-terminal domain — substrate binding site for nicotinamide
- C-terminal domain — S-adenosyl-L-methionine (SAM) binding site
- Active site — catalyzes methyl transfer
The enzyme requires SAM as a methyl donor and produces S-adenosyl-L-homocysteine (SAH) as a byproduct.
NNMT catalyzes:
Nicotinamide + SAM → N-Methylnicotinamide (MNAM) + SAH
- Regulates nicotinamide levels
- Produces N-methylnicotinamide (MNAM)
- MNAM is further metabolized to N-methyl-2-pyridone-5-carboxamide (Me2PY) and N-methyl-4-pyridone-5-carboxamide (Me4PY)
- Links nicotinamide metabolism to folate and methionine cycles
- SAH production affects DNA methylation capacity
- Influences epigenetic regulation
- Elevated NNMT activity in PD brains
- Altered NAD+ metabolite levels
- May affect mitochondrial function
- Potential neuroprotective role of MNAM
- Increased NNMT expression in AD
- Dysregulated one-carbon metabolism
- Elevated homocysteine levels
- Linked to amyloid pathology
- Overexpression in multiple cancer types
- Associated with poor prognosis
- Metabolic reprogramming in cancer cells
NNMT is a potential drug target for:
- Neurodegenerative disease treatment
- Cancer therapy
- Metabolic disorder management
- NNMT: structure, function, and therapeutic potential
- NAD+ metabolism in Parkinson's disease
- NNMT in cancer metabolism