IDP2
S. cerevisiae
isocitrate dehydrogenase (NADP(+)) IDP2
What the model saw
Gene: IDP2 Organism: Saccharomyces cerevisiae Known functions: isocitrate dehydrogenase (NADP(+)) IDP2. 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(+)) IDP2. 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
IDP2 encodes the peroxisomal/cytosolic NADP+-dependent isocitrate dehydrogenase in S. cerevisiae, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while reducing NADP+ to NADPH. This reaction sits at a critical metabolic node: it generates NADPH, a key reductant for antioxidant defense (e.g., glutathione and thioredoxin systems), and produces alpha-ketoglutarate, a TCA cycle intermediate and cofactor for alpha-KG-dependent dioxygenases including histone and DNA demethylases. Elevated cytosolic NADPH production supports redox homeostasis and resistance to oxidative stress, which is a well-established pro-longevity mechanism in yeast. Additionally, IDP2 is upregulated during caloric restriction and gluconeogenic growth conditions, linking it to nutrient-sensing pathways that extend lifespan. The generation of alpha-ketoglutarate also feeds into nitrogen metabolism and TOR signaling modulation, further connecting IDP2 activity to longevity-associated nutrient sensing networks.
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-sounding but ultimately incorrect. While IDP2 does encode an NADP+-dependent isocitrate dehydrogenase and the biochemical functions described are accurate, the model incorrectly inferred that these functions would make IDP2 pro-longevity. In reality, IDP2 is anti-longevity in yeast. The model's reasoning about NADPH production supporting antioxidant defense and caloric restriction connections is speculative and not grounded in actual experimental evidence about IDP2's role in yeast aging. The model was fairly confident (0.72) in the wrong direction.
Raw API responses
solver
{
"reasoning": "IDP2 encodes the peroxisomal/cytosolic NADP+-dependent isocitrate dehydrogenase in S. cerevisiae, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while reducing NADP+ to NADPH. This reaction sits at a critical metabolic node: it generates NADPH, a key reductant for antioxidant defense (e.g., glutathione and thioredoxin systems), and produces alpha-ketoglutarate, a TCA cycle intermediate and cofactor for alpha-KG-dependent dioxygenases including histone and DNA demethylases. Elevated cytosolic NADPH production supports redox homeostasis and resistance to oxidative stress, which is a well-established pro-longevity mechanism in yeast. Additionally, IDP2 is upregulated during caloric restriction and gluconeogenic growth conditions, linking it to nutrient-sensing pathways that extend lifespan. The generation of alpha-ketoglutarate also feeds into nitrogen metabolism and TOR signaling modulation, further connecting IDP2 activity to longevity-associated nutrient sensing networks.",
"confidence": 0.72,
"key_pathways": [
"NADPH-dependent redox homeostasis and antioxidant defense",
"TCA cycle / alpha-ketoglutarate metabolism",
"Caloric restriction and nutrient sensing (TOR pathway)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"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-sounding but ultimately incorrect. While IDP2 does encode an NADP+-dependent isocitrate dehydrogenase and the biochemical functions described are accurate, the model incorrectly inferred that these functions would make IDP2 pro-longevity. In reality, IDP2 is anti-longevity in yeast. The model's reasoning about NADPH production supporting antioxidant defense and caloric restriction connections is speculative and not grounded in actual experimental evidence about IDP2's role in yeast aging. The model was fairly confident (0.72) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}