ADE1
S. cerevisiae
phosphoribosylaminoimidazolesuccinocarboxamide synthase
What the model saw
Gene: ADE1 Organism: Saccharomyces cerevisiae Known functions: phosphoribosylaminoimidazolesuccinocarboxamide synthase. phosphoribosylaminoimidazolesuccinocarboxamide synthase activity. protein binding.
View unredacted entry
phosphoribosylaminoimidazolesuccinocarboxamide synthase. phosphoribosylaminoimidazolesuccinocarboxamide synthase activity. protein binding.
Solver output
ADE1 encodes phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR) synthase, which catalyzes the eighth step of the de novo purine biosynthesis pathway. Adequate purine (adenine/AMP) availability is essential for maintaining AMPK activity and energy sensing; disruption of this pathway leads to adenine auxotrophy and accumulation of toxic intermediates (e.g., red pigment from AIR accumulation), causing cellular stress. In yeast, adenine limitation and purine pathway dysfunction are well-known to impair chronological and replicative lifespan, partly through effects on NAD+ metabolism, TORC1 nutrient sensing, and proteostasis. Functional ADE1 ensures sufficient purine pools to support nucleotide-dependent signaling (including AMPK/Snf1 activation) and prevents toxic metabolite accumulation, thereby supporting longevity. The connection to nutrient sensing via purine/AMP levels places this gene squarely in the deregulated nutrient-sensing hallmark.
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 while the ground truth is anti_longevity. The model's reasoning is plausible on the surface (ADE1 supports purine biosynthesis, which supports cellular function), but it gets the direction wrong. In yeast aging research, ADE1 is classified as anti_longevity, meaning its deletion or loss extends lifespan. The model's reasoning about ADE1 being necessary for longevity (pro_longevity) is incorrect. The model did correctly identify the purine biosynthesis pathway and some relevant connections (AMPK/Snf1, nutrient sensing), but drew the wrong conclusion about the direction of effect. The model showed moderate confidence (0.62) in the wrong answer.
Raw API responses
solver
{
"reasoning": "ADE1 encodes phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR) synthase, which catalyzes the eighth step of the de novo purine biosynthesis pathway. Adequate purine (adenine/AMP) availability is essential for maintaining AMPK activity and energy sensing; disruption of this pathway leads to adenine auxotrophy and accumulation of toxic intermediates (e.g., red pigment from AIR accumulation), causing cellular stress. In yeast, adenine limitation and purine pathway dysfunction are well-known to impair chronological and replicative lifespan, partly through effects on NAD+ metabolism, TORC1 nutrient sensing, and proteostasis. Functional ADE1 ensures sufficient purine pools to support nucleotide-dependent signaling (including AMPK/Snf1 activation) and prevents toxic metabolite accumulation, thereby supporting longevity. The connection to nutrient sensing via purine/AMP levels places this gene squarely in the deregulated nutrient-sensing hallmark.",
"confidence": 0.62,
"key_pathways": [
"de novo purine biosynthesis",
"AMP/AMPK (Snf1) nutrient sensing",
"adenine metabolite homeostasis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity while the ground truth is anti_longevity. The model's reasoning is plausible on the surface (ADE1 supports purine biosynthesis, which supports cellular function), but it gets the direction wrong. In yeast aging research, ADE1 is classified as anti_longevity, meaning its deletion or loss extends lifespan. The model's reasoning about ADE1 being necessary for longevity (pro_longevity) is incorrect. The model did correctly identify the purine biosynthesis pathway and some relevant connections (AMPK/Snf1, nutrient sensing), but drew the wrong conclusion about the direction of effect. The model showed moderate confidence (0.62) in the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}