NNMT (Nicotinamide N-methyltransferase) encodes an enzyme that catalyzes the N-methylation of nicotinamide and other pyridine compounds. This enzyme plays a crucial role in NAD+ metabolism and one-carbon metabolism, with significant implications for neurodegeneration and aging.
| Attribute |
Value |
| Gene Symbol |
NNMT |
| Full Name |
Nicotinamide N-methyltransferase |
| Chromosomal Location |
11q13.2 |
| NCBI Gene ID |
4837 |
| Ensembl ID |
ENSG00000166741 |
| UniProt ID |
P40261 |
| Associated Diseases |
Parkinson's disease, Alzheimer's disease, cancer, metabolic disorders |
NNMT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to nicotinamide, producing N-methylnicotinamide (MNAM) and S-adenosyl-L-homocysteine (SAH). This reaction is part of the one-carbon metabolism pathway and has several important implications:
- NAD+ metabolite regulation — MNAM is further metabolized to N-methyl-2-pyridone-5-carboxamide (Me2PY) and N-methyl-4-pyridone-5-carboxamide (Me4PY), which are excreted in urine
- One-carbon metabolism — links nicotinamide metabolism to folate and methionine cycles
- Epigenetic regulation — SAH is a potent inhibitor of DNA methyltransferases
- Cellular energetics — affects NAD+ availability for sirtuins and other NAD+-dependent enzymes
NNMT is expressed in various brain regions:
- Cerebral cortex
- Hippocampus
- Substantia nigra
- Cerebellum
- Astrocytes and neurons
Parkinson's Disease:
- NNMT activity is elevated in Parkinson's disease brains
- MNAM may have neuroprotective effects by enhancing mitochondrial function
- Altered NAD+ metabolism contributes to dopaminergic neuron vulnerability
Alzheimer's Disease:
- NNMT is upregulated in AD brains
- Changes in one-carbon metabolism affect homocysteine levels
- Linked to amyloid-beta toxicity and tau pathology
- Type 2 diabetes
- Non-alcoholic fatty liver disease
- Obesity
- Overexpression in multiple cancer types
- Associated with poor prognosis
- Potential therapeutic target
NNMT modulators are being explored for:
- Neurodegenerative disease treatment
- Cancer therapy
- Metabolic disorder management
- NNMT: a potential therapeutic target for neurodegenerative diseases
- Nicotinamide N-methyltransferase: structure, function, and therapeutic applications
- NAD+ metabolism in Parkinson's disease
- One-carbon metabolism and Alzheimer's disease