Nadsyn
D. melanogaster
NAD synthetase
What the model saw
Gene: Nadsyn Organism: Drosophila melanogaster Known functions: NAD synthetase. ATP binding. NAD+ synthase (glutamine-hydrolyzing) activity. glutaminase activity.
View unredacted entry
NAD synthetase. ATP binding. NAD+ synthase (glutamine-hydrolyzing) activity. glutaminase activity.
Solver output
Nadsyn encodes NAD synthetase, the final enzyme in the NAD+ biosynthesis pathway, catalyzing the ATP-dependent conversion of nicotinic acid adenine dinucleotide (NaAD) to NAD+ using glutamine as the nitrogen donor (via its glutaminase activity). NAD+ is a critical coenzyme and signaling molecule that serves as a substrate for sirtuins (e.g., Sir2 in Drosophila) and PARP enzymes, both of which are central regulators of aging, DNA repair, and metabolic homeostasis. Declining NAD+ levels are a hallmark of aging across species, and boosting NAD+ biosynthesis extends lifespan in multiple model organisms. By maintaining intracellular NAD+ pools, Nadsyn supports sirtuin-mediated deacetylation of metabolic and stress-response targets, linking it directly to nutrient sensing and longevity pathways. Loss of Nadsyn function would be expected to reduce NAD+ availability, impairing sirtuin activity and accelerating aging phenotypes.
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 pro_longevity for Nadsyn in Drosophila melanogaster with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies Nadsyn as NAD synthetase catalyzing the final step of NAD+ biosynthesis, explains the role of NAD+ as a sirtuin substrate, notes the well-established connection between NAD+ levels and aging, and correctly predicts that maintaining NAD+ pools via Nadsyn supports longevity. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization given the sirtuin/metabolic regulation angle, though "metabolic regulation" might be more precise. Overall, the reasoning is thorough, accurate, and well-supported by the literature.
Raw API responses
solver
{
"reasoning": "Nadsyn encodes NAD synthetase, the final enzyme in the NAD+ biosynthesis pathway, catalyzing the ATP-dependent conversion of nicotinic acid adenine dinucleotide (NaAD) to NAD+ using glutamine as the nitrogen donor (via its glutaminase activity). NAD+ is a critical coenzyme and signaling molecule that serves as a substrate for sirtuins (e.g., Sir2 in Drosophila) and PARP enzymes, both of which are central regulators of aging, DNA repair, and metabolic homeostasis. Declining NAD+ levels are a hallmark of aging across species, and boosting NAD+ biosynthesis extends lifespan in multiple model organisms. By maintaining intracellular NAD+ pools, Nadsyn supports sirtuin-mediated deacetylation of metabolic and stress-response targets, linking it directly to nutrient sensing and longevity pathways. Loss of Nadsyn function would be expected to reduce NAD+ availability, impairing sirtuin activity and accelerating aging phenotypes.",
"confidence": 0.82,
"key_pathways": [
"NAD+ biosynthesis (de novo/salvage pathway)",
"Sirtuin (Sir2) signaling and deacetylation",
"NAD+-dependent metabolic regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Nadsyn in Drosophila melanogaster with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies Nadsyn as NAD synthetase catalyzing the final step of NAD+ biosynthesis, explains the role of NAD+ as a sirtuin substrate, notes the well-established connection between NAD+ levels and aging, and correctly predicts that maintaining NAD+ pools via Nadsyn supports longevity. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization given the sirtuin/metabolic regulation angle, though \"metabolic regulation\" might be more precise. Overall, the reasoning is thorough, accurate, and well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}