tdo-2
C. elegans
Tryptophan 2,3-dioxygenase
What the model saw
Gene: tdo-2 Organism: Caenorhabditis elegans Known functions: Tryptophan 2,3-dioxygenase. L-tryptophan 2,3-dioxygenase activity. heme binding. metal ion binding.
View unredacted entry
Tryptophan 2,3-dioxygenase. L-tryptophan 2,3-dioxygenase activity. heme binding. metal ion binding.
Solver output
TDO-2 (Tryptophan 2,3-dioxygenase) catalyzes the first and rate-limiting step of the kynurenine pathway, converting L-tryptophan into N-formylkynurenine. This diverts tryptophan away from serotonin and other beneficial metabolites toward kynurenine pathway products. In C. elegans, tryptophan is also a precursor to indole derivatives that can activate the aryl hydrocarbon receptor (AHR-1) and influence DAF-16/FOXO signaling. Critically, tryptophan catabolism via TDO-2 reduces the availability of tryptophan for NAD+ biosynthesis through the kynurenine route in a context-dependent manner, and kynurenine pathway metabolites have been shown to suppress DAF-16 nuclear localization, thereby antagonizing insulin/IGF-1 signaling-mediated longevity. RNAi knockdown of tdo-2 in C. elegans has been demonstrated to extend lifespan, consistent with its normal function being anti-longevity by depleting tryptophan and generating kynurenine metabolites that dampen stress resistance pathways.
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 identifies tdo-2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is largely correct: TDO-2 catalyzes the first step of the kynurenine pathway, and RNAi knockdown of tdo-2 extends lifespan in C. elegans. The model correctly notes that kynurenine pathway metabolites suppress DAF-16 nuclear localization. Some details are slightly speculative (e.g., the specific role of AHR-1 signaling and NAD+ biosynthesis context), but the core mechanism is well-supported. The mechanism_class of "deregulated_nutrient_sensing" is a reasonable but imperfect categorization — tryptophan catabolism/kynurenine pathway would be more precise. Overall, solid reasoning with correct conclusion.
Raw API responses
solver
{
"reasoning": "TDO-2 (Tryptophan 2,3-dioxygenase) catalyzes the first and rate-limiting step of the kynurenine pathway, converting L-tryptophan into N-formylkynurenine. This diverts tryptophan away from serotonin and other beneficial metabolites toward kynurenine pathway products. In C. elegans, tryptophan is also a precursor to indole derivatives that can activate the aryl hydrocarbon receptor (AHR-1) and influence DAF-16/FOXO signaling. Critically, tryptophan catabolism via TDO-2 reduces the availability of tryptophan for NAD+ biosynthesis through the kynurenine route in a context-dependent manner, and kynurenine pathway metabolites have been shown to suppress DAF-16 nuclear localization, thereby antagonizing insulin/IGF-1 signaling-mediated longevity. RNAi knockdown of tdo-2 in C. elegans has been demonstrated to extend lifespan, consistent with its normal function being anti-longevity by depleting tryptophan and generating kynurenine metabolites that dampen stress resistance pathways.",
"confidence": 0.82,
"key_pathways": [
"kynurenine pathway / tryptophan catabolism",
"DAF-16/FOXO insulin-IGF-1 signaling",
"aryl hydrocarbon receptor (AHR-1) signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies tdo-2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is largely correct: TDO-2 catalyzes the first step of the kynurenine pathway, and RNAi knockdown of tdo-2 extends lifespan in C. elegans. The model correctly notes that kynurenine pathway metabolites suppress DAF-16 nuclear localization. Some details are slightly speculative (e.g., the specific role of AHR-1 signaling and NAD+ biosynthesis context), but the core mechanism is well-supported. The mechanism_class of \"deregulated_nutrient_sensing\" is a reasonable but imperfect categorization — tryptophan catabolism/kynurenine pathway would be more precise. Overall, solid reasoning with correct conclusion.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}