ALD6
S. cerevisiae
aldehyde dehydrogenase (NADP(+)) ALD6
What the model saw
Gene: ALD6 Organism: Saccharomyces cerevisiae Known functions: aldehyde dehydrogenase (NADP(+)) ALD6. acetaldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase (NAD+) activity. aldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase [NAD(P)+] activity. oxidoreductase activity.
View unredacted entry
aldehyde dehydrogenase (NADP(+)) ALD6. acetaldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase (NAD+) activity. aldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase [NAD(P)+] activity. oxidoreductase activity.
Solver output
ALD6 encodes a cytosolic NADP+-dependent aldehyde dehydrogenase that catalyzes the oxidation of acetaldehyde to acetate, thereby detoxifying reactive aldehyde species. Acetaldehyde is a highly reactive and toxic byproduct of ethanol metabolism that can form adducts with proteins and DNA, causing oxidative damage. By efficiently clearing acetaldehyde and other reactive aldehydes, ALD6 reduces proteotoxic and genotoxic stress. Additionally, the NADP+-dependent reaction generates NADPH, which is a key reducing equivalent supporting antioxidant defenses (e.g., glutathione and thioredoxin systems). Reduced aldehyde-driven oxidative damage and enhanced NADPH availability together support cellular redox homeostasis and proteostasis, both of which are associated with extended 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 but the ground truth is anti_longevity. The model's reasoning was plausible on the surface (acetaldehyde detoxification, NADPH generation supporting antioxidant defenses), but it reached the wrong conclusion. In yeast, ALD6 deletion has been shown to extend lifespan, meaning ALD6 activity is anti-longevity. The model's mechanistic reasoning about detoxification and NADPH generation is the kind of reasoning that sounds compelling but misses the actual biology - ALD6 may compete with other metabolic pathways or its activity may reduce flux through longevity-promoting pathways. The model had moderate confidence (0.65) but was still wrong on both the answer and the underlying mechanism. The mechanism_class of "mitochondrial_dysfunction" is also incorrect since ALD6 is a cytosolic enzyme and the relevant mechanism is not mitochondrial dysfunction.
Raw API responses
solver
{
"reasoning": "ALD6 encodes a cytosolic NADP+-dependent aldehyde dehydrogenase that catalyzes the oxidation of acetaldehyde to acetate, thereby detoxifying reactive aldehyde species. Acetaldehyde is a highly reactive and toxic byproduct of ethanol metabolism that can form adducts with proteins and DNA, causing oxidative damage. By efficiently clearing acetaldehyde and other reactive aldehydes, ALD6 reduces proteotoxic and genotoxic stress. Additionally, the NADP+-dependent reaction generates NADPH, which is a key reducing equivalent supporting antioxidant defenses (e.g., glutathione and thioredoxin systems). Reduced aldehyde-driven oxidative damage and enhanced NADPH availability together support cellular redox homeostasis and proteostasis, both of which are associated with extended lifespan in yeast.",
"confidence": 0.65,
"key_pathways": [
"acetaldehyde/aldehyde detoxification",
"NADPH regeneration and redox homeostasis",
"oxidative stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning was plausible on the surface (acetaldehyde detoxification, NADPH generation supporting antioxidant defenses), but it reached the wrong conclusion. In yeast, ALD6 deletion has been shown to extend lifespan, meaning ALD6 activity is anti-longevity. The model's mechanistic reasoning about detoxification and NADPH generation is the kind of reasoning that sounds compelling but misses the actual biology - ALD6 may compete with other metabolic pathways or its activity may reduce flux through longevity-promoting pathways. The model had moderate confidence (0.65) but was still wrong on both the answer and the underlying mechanism. The mechanism_class of \"mitochondrial_dysfunction\" is also incorrect since ALD6 is a cytosolic enzyme and the relevant mechanism is not mitochondrial dysfunction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}