acox-3
C. elegans
Acyl-coenzyme A oxidase acox-3
What the model saw
Gene: acox-3 Organism: Caenorhabditis elegans Known functions: Acyl-coenzyme A oxidase acox-3. ATP binding. FAD binding. acyl-CoA oxidase activity. fatty acid binding. flavin adenine dinucleotide binding. oxidoreductase activity, acting on the CH-CH group of donors. pristanoyl-CoA oxidase activity.
View unredacted entry
Acyl-coenzyme A oxidase acox-3. ATP binding. FAD binding. acyl-CoA oxidase activity. fatty acid binding. flavin adenine dinucleotide binding. oxidoreductase activity, acting on the CH-CH group of donors. pristanoyl-CoA oxidase activity.
Solver output
acox-3 encodes a peroxisomal acyl-CoA oxidase (specifically with pristanoyl-CoA oxidase activity) that catalyzes the first and rate-limiting step of peroxisomal fatty acid β-oxidation, using FAD as a cofactor and generating H₂O₂ as a byproduct. In C. elegans, peroxisomal fatty acid oxidation is linked to lipid metabolism and nutrient sensing pathways that intersect with IIS and AMPK signaling. On one hand, enhanced fatty acid oxidation can promote longevity by reducing lipid accumulation and supporting metabolic flexibility (pro-longevity); on the other hand, the H₂O₂ generated as a byproduct of acyl-CoA oxidase activity can contribute to oxidative stress (anti-longevity). acox-3's specificity for branched-chain substrates (pristanoyl-CoA) rather than straight-chain fatty acids makes its net contribution to longevity ambiguous compared to the more studied acox-1/acox-2 paralogs, and its precise role in C. elegans lifespan has not been clearly resolved in the literature.
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 "unclear" while the ground truth is "anti_longevity." The model's reasoning was overly hedged and failed to commit to the correct answer. The model did mention H₂O₂ generation as a potential anti-longevity mechanism, which is partially relevant, but it balanced this against pro-longevity arguments and concluded the effect was ambiguous. The actual classification is anti_longevity, suggesting that acox-3 promotes aging (i.e., its loss extends lifespan or its activity is detrimental). The model's mechanistic reasoning touched on the right pathway (ROS/H₂O₂ generation) but failed to identify the dominant direction. The confidence of 0.42 reflects appropriate uncertainty, but the final answer was still wrong. The reasoning quality is low because it failed to leverage the known anti-longevity role of peroxisomal fatty acid oxidation enzymes in C. elegans.
Raw API responses
solver
{
"reasoning": "acox-3 encodes a peroxisomal acyl-CoA oxidase (specifically with pristanoyl-CoA oxidase activity) that catalyzes the first and rate-limiting step of peroxisomal fatty acid β-oxidation, using FAD as a cofactor and generating H₂O₂ as a byproduct. In C. elegans, peroxisomal fatty acid oxidation is linked to lipid metabolism and nutrient sensing pathways that intersect with IIS and AMPK signaling. On one hand, enhanced fatty acid oxidation can promote longevity by reducing lipid accumulation and supporting metabolic flexibility (pro-longevity); on the other hand, the H₂O₂ generated as a byproduct of acyl-CoA oxidase activity can contribute to oxidative stress (anti-longevity). acox-3's specificity for branched-chain substrates (pristanoyl-CoA) rather than straight-chain fatty acids makes its net contribution to longevity ambiguous compared to the more studied acox-1/acox-2 paralogs, and its precise role in C. elegans lifespan has not been clearly resolved in the literature.",
"confidence": 0.42,
"key_pathways": [
"peroxisomal fatty acid beta-oxidation",
"lipid metabolism and nutrient sensing (IIS/AMPK)",
"reactive oxygen species generation (H2O2 byproduct)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning was overly hedged and failed to commit to the correct answer. The model did mention H₂O₂ generation as a potential anti-longevity mechanism, which is partially relevant, but it balanced this against pro-longevity arguments and concluded the effect was ambiguous. The actual classification is anti_longevity, suggesting that acox-3 promotes aging (i.e., its loss extends lifespan or its activity is detrimental). The model's mechanistic reasoning touched on the right pathway (ROS/H₂O₂ generation) but failed to identify the dominant direction. The confidence of 0.42 reflects appropriate uncertainty, but the final answer was still wrong. The reasoning quality is low because it failed to leverage the known anti-longevity role of peroxisomal fatty acid oxidation enzymes in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}