gpd-3
C. elegans
Glyceraldehyde-3-phosphate dehydrogenase 3
What the model saw
Gene: gpd-3 Organism: Caenorhabditis elegans Known functions: Glyceraldehyde-3-phosphate dehydrogenase 3. NAD binding. NADP binding. glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity. oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor.
View unredacted entry
Glyceraldehyde-3-phosphate dehydrogenase 3. NAD binding. NADP binding. glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity. oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor.
Solver output
gpd-3 encodes a glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a central glycolytic enzyme that catalyzes the NAD⁺-dependent oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. Elevated glycolytic flux through GAPDH promotes glucose catabolism and energy production via fermentation-like metabolism, which in C. elegans is associated with shortened lifespan compared to oxidative/mitochondrial metabolism. In the context of nutrient sensing, high glycolytic activity suppresses pathways such as AMPK and DAF-16/FOXO that are pro-longevity, and promotes insulin/IGF-1-like signaling tone. Studies in C. elegans have shown that reducing glycolysis (e.g., by inhibiting glycolytic enzymes) can extend lifespan by shifting metabolism toward mitochondrial respiration and activating stress-response pathways. Additionally, GAPDH consumes NAD⁺, reducing the NAD⁺/NADH ratio, which can dampen sirtuin (sir-2.1) activity—a known pro-longevity deacetylase in worms. Thus, the normal pro-glycolytic function of gpd-3 is predicted to be anti-longevity.
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 gpd-3. The mechanistic reasoning is plausible and well-constructed: GAPDH promotes glycolytic flux, consumes NAD+, suppresses pro-longevity pathways (DAF-16/FOXO, sirtuins, AMPK), and studies in C. elegans support that reducing glycolysis extends lifespan. The reasoning is coherent and consistent with known biology. Confidence of 0.62 is appropriately moderate. The mechanism class "deregulated_nutrient_sensing" is reasonable though glycolysis/metabolic flux might be more precise. Overall a solid prediction with good mechanistic support.
Raw API responses
solver
{
"reasoning": "gpd-3 encodes a glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a central glycolytic enzyme that catalyzes the NAD⁺-dependent oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate. Elevated glycolytic flux through GAPDH promotes glucose catabolism and energy production via fermentation-like metabolism, which in C. elegans is associated with shortened lifespan compared to oxidative/mitochondrial metabolism. In the context of nutrient sensing, high glycolytic activity suppresses pathways such as AMPK and DAF-16/FOXO that are pro-longevity, and promotes insulin/IGF-1-like signaling tone. Studies in C. elegans have shown that reducing glycolysis (e.g., by inhibiting glycolytic enzymes) can extend lifespan by shifting metabolism toward mitochondrial respiration and activating stress-response pathways. Additionally, GAPDH consumes NAD⁺, reducing the NAD⁺/NADH ratio, which can dampen sirtuin (sir-2.1) activity—a known pro-longevity deacetylase in worms. Thus, the normal pro-glycolytic function of gpd-3 is predicted to be anti-longevity.",
"confidence": 0.62,
"key_pathways": [
"glycolysis / NAD+ consumption",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"NAD+-dependent sirtuin (sir-2.1) activity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for gpd-3. The mechanistic reasoning is plausible and well-constructed: GAPDH promotes glycolytic flux, consumes NAD+, suppresses pro-longevity pathways (DAF-16/FOXO, sirtuins, AMPK), and studies in C. elegans support that reducing glycolysis extends lifespan. The reasoning is coherent and consistent with known biology. Confidence of 0.62 is appropriately moderate. The mechanism class \"deregulated_nutrient_sensing\" is reasonable though glycolysis/metabolic flux might be more precise. Overall a solid prediction with good mechanistic support.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}