pck-2
C. elegans
Phosphoenolpyruvate carboxykinase
What the model saw
Gene: pck-2 Organism: Caenorhabditis elegans Known functions: Phosphoenolpyruvate carboxykinase. GTP binding. manganese ion binding. phosphoenolpyruvate carboxykinase (GTP) activity. phosphoenolpyruvate carboxykinase activity. purine nucleotide binding.
View unredacted entry
Phosphoenolpyruvate carboxykinase. GTP binding. manganese ion binding. phosphoenolpyruvate carboxykinase (GTP) activity. phosphoenolpyruvate carboxykinase activity. purine nucleotide binding.
Solver output
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step of gluconeogenesis, converting oxaloacetate to phosphoenolpyruvate using GTP, and is a central node in carbon metabolism and energy homeostasis. In C. elegans, pck-2 (mitochondrial PEPCK) has been shown to support longevity by promoting gluconeogenesis and anaplerotic flux, which sustains metabolic flexibility under nutrient-limiting conditions. Upregulation of PEPCK activity is associated with dietary restriction-like metabolic states that extend lifespan, linking it to the nutrient-sensing axis (IIS/FOXO and AMPK pathways). The GTP-dependent activity and manganese ion binding are hallmarks of the mitochondrial isoform, which feeds into TCA cycle replenishment and supports mitochondrial energy metabolism. Loss of pck-2 in C. elegans impairs gluconeogenesis and reduces lifespan, consistent with a pro-longevity role.
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 confidently states that "loss of pck-2 in C. elegans impairs gluconeogenesis and reduces lifespan," which is the opposite of what the GenAge database records. In reality, pck-2 appears to be anti-longevity, meaning its activity/expression shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning about PEPCK's role in gluconeogenesis and metabolic flexibility is plausible in general terms, but the conclusion drawn about the direction of effect is wrong. The model was moderately confident (0.72) in an incorrect answer, and the specific claim about loss-of-function reducing lifespan appears to be a hallucinated or incorrect factual assertion.
Raw API responses
solver
{
"reasoning": "Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step of gluconeogenesis, converting oxaloacetate to phosphoenolpyruvate using GTP, and is a central node in carbon metabolism and energy homeostasis. In C. elegans, pck-2 (mitochondrial PEPCK) has been shown to support longevity by promoting gluconeogenesis and anaplerotic flux, which sustains metabolic flexibility under nutrient-limiting conditions. Upregulation of PEPCK activity is associated with dietary restriction-like metabolic states that extend lifespan, linking it to the nutrient-sensing axis (IIS/FOXO and AMPK pathways). The GTP-dependent activity and manganese ion binding are hallmarks of the mitochondrial isoform, which feeds into TCA cycle replenishment and supports mitochondrial energy metabolism. Loss of pck-2 in C. elegans impairs gluconeogenesis and reduces lifespan, consistent with a pro-longevity role.",
"confidence": 0.72,
"key_pathways": [
"gluconeogenesis / PEPCK-mediated carbon flux",
"nutrient sensing (IIS/FOXO, AMPK)",
"TCA cycle anaplerosis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning confidently states that \"loss of pck-2 in C. elegans impairs gluconeogenesis and reduces lifespan,\" which is the opposite of what the GenAge database records. In reality, pck-2 appears to be anti-longevity, meaning its activity/expression shortens lifespan (or its loss extends lifespan). The model's mechanistic reasoning about PEPCK's role in gluconeogenesis and metabolic flexibility is plausible in general terms, but the conclusion drawn about the direction of effect is wrong. The model was moderately confident (0.72) in an incorrect answer, and the specific claim about loss-of-function reducing lifespan appears to be a hallucinated or incorrect factual assertion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}