GRE3
S. cerevisiae
trifunctional aldehyde reductase/xylose reductase/glucose 1-dehydrogenase (NADP(+))
What the model saw
Gene: GRE3 Organism: Saccharomyces cerevisiae Known functions: trifunctional aldehyde reductase/xylose reductase/glucose 1-dehydrogenase (NADP(+)). D-xylose reductase (NADPH) activity. aldose reductase (NADPH) activity. mRNA binding. oxidoreductase activity.
View unredacted entry
trifunctional aldehyde reductase/xylose reductase/glucose 1-dehydrogenase (NADP(+)). D-xylose reductase (NADPH) activity. aldose reductase (NADPH) activity. mRNA binding. oxidoreductase activity.
Solver output
GRE3 encodes an NADPH-dependent aldose/xylose reductase that reduces aldoses (including glucose-derived aldehydes and xylose) to their corresponding sugar alcohols (e.g., xylitol, sorbitol). This activity consumes NADPH, a key currency for reductive biosynthesis and antioxidant defense (glutathione recycling). Elevated aldose reductase activity is associated with the polyol pathway, which in the context of high glucose diverts carbon flux toward sugar alcohols, perturbs NADPH/NADP+ balance, and can generate osmotic stress and reactive intermediates. In yeast, GRE3 is induced under osmotic and oxidative stress but its constitutive or elevated activity under nutrient-rich conditions would deplete NADPH and potentially impair redox homeostasis and caloric-restriction-like signaling. Loss of GRE3 in yeast has been reported to extend chronological lifespan, consistent with the polyol pathway being detrimental under standard glucose conditions. The gene's role in glucose metabolism and NADPH consumption places it within the deregulated nutrient-sensing hallmark.
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 GRE3. The mechanistic reasoning is plausible and well-constructed: GRE3's NADPH-consuming aldose reductase activity depletes NADPH needed for antioxidant defense, and loss of GRE3 extends chronological lifespan. The model correctly identifies the polyol pathway and NADPH/NADP+ balance as key mechanisms. The mechanism_class of "deregulated_nutrient_sensing" is a reasonable categorization, though "redox_homeostasis" might be more precise. The confidence of 0.62 is appropriately calibrated. Overall solid reasoning with correct answer.
Raw API responses
solver
{
"reasoning": "GRE3 encodes an NADPH-dependent aldose/xylose reductase that reduces aldoses (including glucose-derived aldehydes and xylose) to their corresponding sugar alcohols (e.g., xylitol, sorbitol). This activity consumes NADPH, a key currency for reductive biosynthesis and antioxidant defense (glutathione recycling). Elevated aldose reductase activity is associated with the polyol pathway, which in the context of high glucose diverts carbon flux toward sugar alcohols, perturbs NADPH/NADP+ balance, and can generate osmotic stress and reactive intermediates. In yeast, GRE3 is induced under osmotic and oxidative stress but its constitutive or elevated activity under nutrient-rich conditions would deplete NADPH and potentially impair redox homeostasis and caloric-restriction-like signaling. Loss of GRE3 in yeast has been reported to extend chronological lifespan, consistent with the polyol pathway being detrimental under standard glucose conditions. The gene's role in glucose metabolism and NADPH consumption places it within the deregulated nutrient-sensing hallmark.",
"confidence": 0.62,
"key_pathways": [
"polyol/aldose reductase pathway (NADPH consumption)",
"osmotic stress response",
"redox homeostasis (NADPH/NADP+ balance)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for GRE3. The mechanistic reasoning is plausible and well-constructed: GRE3's NADPH-consuming aldose reductase activity depletes NADPH needed for antioxidant defense, and loss of GRE3 extends chronological lifespan. The model correctly identifies the polyol pathway and NADPH/NADP+ balance as key mechanisms. The mechanism_class of \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"redox_homeostasis\" might be more precise. The confidence of 0.62 is appropriately calibrated. Overall solid reasoning with correct answer.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}