anmt-1
C. elegans
Nicotinamide N-methyltransferase
What the model saw
Gene: anmt-1 Organism: Caenorhabditis elegans Known functions: Nicotinamide N-methyltransferase. N-methyltransferase activity. methyltransferase activity. nicotinamide N-methyltransferase activity.
View unredacted entry
Nicotinamide N-methyltransferase. N-methyltransferase activity. methyltransferase activity. nicotinamide N-methyltransferase activity.
Solver output
Nicotinamide N-methyltransferase (NNMT/anmt-1) catalyzes the methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA), consuming NAM as a substrate. NAM is a precursor for NAD+ biosynthesis via the salvage pathway; by diverting NAM away from NAD+ production, NNMT activity reduces intracellular NAD+ levels. NAD+ is a critical cofactor for sirtuins (e.g., SIR-2.1 in C. elegans) and other longevity-associated enzymes; lower NAD+ impairs sirtuin-mediated deacetylation and downstream stress-response and metabolic regulation. Additionally, the methylation reaction consumes S-adenosylmethionine (SAM), depleting the methyl donor pool and potentially disrupting epigenetic methylation balance. Loss-of-function of anmt-1 in C. elegans has been associated with extended lifespan, consistent with the idea that its normal activity is detrimental to longevity by limiting NAD+ availability and sirtuin signaling.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted anti_longevity for anmt-1 in C. elegans. The mechanistic reasoning is well-grounded: NNMT/anmt-1 methylates nicotinamide (NAM), diverting it from NAD+ biosynthesis, thereby reducing NAD+ levels and impairing sirtuin signaling. The model also correctly notes SAM depletion as a secondary effect. The reasoning that loss-of-function of anmt-1 extends lifespan (making it anti-longevity when active) is consistent with published literature on NNMT in C. elegans. Confidence of 0.78 is appropriate. Overall, this is an excellent prediction with correct answer and sound mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "Nicotinamide N-methyltransferase (NNMT/anmt-1) catalyzes the methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA), consuming NAM as a substrate. NAM is a precursor for NAD+ biosynthesis via the salvage pathway; by diverting NAM away from NAD+ production, NNMT activity reduces intracellular NAD+ levels. NAD+ is a critical cofactor for sirtuins (e.g., SIR-2.1 in C. elegans) and other longevity-associated enzymes; lower NAD+ impairs sirtuin-mediated deacetylation and downstream stress-response and metabolic regulation. Additionally, the methylation reaction consumes S-adenosylmethionine (SAM), depleting the methyl donor pool and potentially disrupting epigenetic methylation balance. Loss-of-function of anmt-1 in C. elegans has been associated with extended lifespan, consistent with the idea that its normal activity is detrimental to longevity by limiting NAD+ availability and sirtuin signaling.",
"confidence": 0.78,
"key_pathways": [
"NAD+ salvage pathway / sirtuin signaling",
"S-adenosylmethionine (SAM) methyl donor metabolism",
"nicotinamide methylation (NAM to 1-methylnicotinamide)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for anmt-1 in C. elegans. The mechanistic reasoning is well-grounded: NNMT/anmt-1 methylates nicotinamide (NAM), diverting it from NAD+ biosynthesis, thereby reducing NAD+ levels and impairing sirtuin signaling. The model also correctly notes SAM depletion as a secondary effect. The reasoning that loss-of-function of anmt-1 extends lifespan (making it anti-longevity when active) is consistent with published literature on NNMT in C. elegans. Confidence of 0.78 is appropriate. Overall, this is an excellent prediction with correct answer and sound mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}