Pck1
M. musculus
phosphoenolpyruvate carboxykinase 1, cytosolic
What the model saw
Gene: Pck1 Organism: Mus musculus Known functions: phosphoenolpyruvate carboxykinase 1, cytosolic. phosphoenolpyruvate carboxykinase, cytosolic [GTP]. GDP binding. GTP binding. carboxylic acid binding. magnesium ion binding. manganese ion binding. nucleoside diphosphate kinase activity. phosphoenolpyruvate carboxykinase (GTP) activity. phosphoenolpyruvate carboxykinase activity. protein serine kinase activity (using GTP as donor). purine nucleotide binding.
View unredacted entry
phosphoenolpyruvate carboxykinase 1, cytosolic. phosphoenolpyruvate carboxykinase, cytosolic [GTP]. GDP binding. GTP binding. carboxylic acid binding. magnesium ion binding. manganese ion binding. nucleoside diphosphate kinase activity. phosphoenolpyruvate carboxykinase (GTP) activity. phosphoenolpyruvate carboxykinase activity. protein serine kinase activity (using GTP as donor). purine nucleotide binding.
Solver output
Pck1 encodes cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), the rate-limiting enzyme of gluconeogenesis that converts oxaloacetate to phosphoenolpyruvate using GTP. This positions Pck1 as a central node in glucose homeostasis and metabolic flexibility. Overexpression of Pck1 in mice has been shown to dramatically extend lifespan and healthspan, associated with enhanced mitochondrial biogenesis, increased fatty acid oxidation, and improved energy metabolism — hallmarks of caloric restriction mimicry. By promoting gluconeogenesis and redirecting carbon flux away from glycolysis, Pck1 activity modulates the AMPK/mTOR nutrient-sensing axis in a manner analogous to dietary restriction. Additionally, its GTP-dependent activity links it to mitochondrial TCA cycle flux and energy charge sensing, further supporting metabolic resilience during aging.
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 pro_longevity for Pck1 in Mus musculus. The mechanistic reasoning is accurate and well-grounded: Pck1 overexpression in mice (the famous "super mice" study by Hanson et al.) does indeed extend lifespan and healthspan, associated with enhanced mitochondrial biogenesis, fatty acid oxidation, and metabolic flexibility. The model correctly identifies the PEPCK-C enzyme's role in gluconeogenesis and its connection to nutrient sensing pathways. The confidence level of 0.62 is appropriately calibrated given the specificity of the knowledge required. The reasoning about caloric restriction mimicry and AMPK/mTOR modulation is mechanistically sound.
Raw API responses
solver
{
"reasoning": "Pck1 encodes cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), the rate-limiting enzyme of gluconeogenesis that converts oxaloacetate to phosphoenolpyruvate using GTP. This positions Pck1 as a central node in glucose homeostasis and metabolic flexibility. Overexpression of Pck1 in mice has been shown to dramatically extend lifespan and healthspan, associated with enhanced mitochondrial biogenesis, increased fatty acid oxidation, and improved energy metabolism — hallmarks of caloric restriction mimicry. By promoting gluconeogenesis and redirecting carbon flux away from glycolysis, Pck1 activity modulates the AMPK/mTOR nutrient-sensing axis in a manner analogous to dietary restriction. Additionally, its GTP-dependent activity links it to mitochondrial TCA cycle flux and energy charge sensing, further supporting metabolic resilience during aging.",
"confidence": 0.62,
"key_pathways": [
"gluconeogenesis / PEPCK-mediated carbon flux",
"AMPK-mTOR nutrient sensing",
"mitochondrial fatty acid oxidation and TCA cycle coupling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Pck1 in Mus musculus. The mechanistic reasoning is accurate and well-grounded: Pck1 overexpression in mice (the famous \"super mice\" study by Hanson et al.) does indeed extend lifespan and healthspan, associated with enhanced mitochondrial biogenesis, fatty acid oxidation, and metabolic flexibility. The model correctly identifies the PEPCK-C enzyme's role in gluconeogenesis and its connection to nutrient sensing pathways. The confidence level of 0.62 is appropriately calibrated given the specificity of the knowledge required. The reasoning about caloric restriction mimicry and AMPK/mTOR modulation is mechanistically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}