IDP3
S. cerevisiae
isocitrate dehydrogenase (NADP(+)) IDP3
What the model saw
Gene: IDP3 Organism: Saccharomyces cerevisiae Known functions: isocitrate dehydrogenase (NADP(+)) IDP3. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor.
View unredacted entry
isocitrate dehydrogenase (NADP(+)) IDP3. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor.
Solver output
IDP3 encodes a peroxisomal NADP+-dependent isocitrate dehydrogenase in S. cerevisiae that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, generating NADPH. Peroxisomal NADPH production by IDP3 is critical for maintaining redox balance within the peroxisome, particularly for neutralizing reactive oxygen species generated during fatty acid beta-oxidation. By sustaining peroxisomal antioxidant capacity and supporting efficient lipid metabolism, IDP3 reduces oxidative damage—a key driver of mitochondrial dysfunction and cellular aging. Additionally, alpha-ketoglutarate produced by this reaction is a known pro-longevity metabolite that can inhibit TOR signaling and serve as a cofactor for dioxygenases involved in epigenetic regulation. Loss of peroxisomal redox homeostasis accelerates oxidative stress accumulation, which is associated with shortened replicative and chronological lifespan in yeast.
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 predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — IDP3 does encode a peroxisomal NADP+-dependent isocitrate dehydrogenase, and the biochemical description is largely accurate. However, the model incorrectly extrapolated that peroxisomal NADPH production and alpha-ketoglutarate generation would make IDP3 pro-longevity. The actual GenAge classification is anti_longevity, meaning deletion or loss of IDP3 extends lifespan (or overexpression shortens it). The model failed to consider that IDP3 might have anti-longevity effects, perhaps by competing for isocitrate that could otherwise feed into other pathways, or through other mechanisms. The reasoning about alpha-ketoglutarate and TOR signaling is speculative and not well-supported for this specific peroxisomal enzyme. The model was confidently wrong.
Raw API responses
solver
{
"reasoning": "IDP3 encodes a peroxisomal NADP+-dependent isocitrate dehydrogenase in S. cerevisiae that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, generating NADPH. Peroxisomal NADPH production by IDP3 is critical for maintaining redox balance within the peroxisome, particularly for neutralizing reactive oxygen species generated during fatty acid beta-oxidation. By sustaining peroxisomal antioxidant capacity and supporting efficient lipid metabolism, IDP3 reduces oxidative damage—a key driver of mitochondrial dysfunction and cellular aging. Additionally, alpha-ketoglutarate produced by this reaction is a known pro-longevity metabolite that can inhibit TOR signaling and serve as a cofactor for dioxygenases involved in epigenetic regulation. Loss of peroxisomal redox homeostasis accelerates oxidative stress accumulation, which is associated with shortened replicative and chronological lifespan in yeast.",
"confidence": 0.72,
"key_pathways": [
"peroxisomal NADPH production and redox homeostasis",
"fatty acid beta-oxidation support",
"alpha-ketoglutarate metabolism and TOR signaling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — IDP3 does encode a peroxisomal NADP+-dependent isocitrate dehydrogenase, and the biochemical description is largely accurate. However, the model incorrectly extrapolated that peroxisomal NADPH production and alpha-ketoglutarate generation would make IDP3 pro-longevity. The actual GenAge classification is anti_longevity, meaning deletion or loss of IDP3 extends lifespan (or overexpression shortens it). The model failed to consider that IDP3 might have anti-longevity effects, perhaps by competing for isocitrate that could otherwise feed into other pathways, or through other mechanisms. The reasoning about alpha-ketoglutarate and TOR signaling is speculative and not well-supported for this specific peroxisomal enzyme. The model was confidently wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}