ADE57
S. cerevisiae
bifunctional aminoimidazole ribotide synthase/glycinamide ribotide synthase
What the model saw
Gene: ADE57 Organism: Saccharomyces cerevisiae Known functions: bifunctional aminoimidazole ribotide synthase/glycinamide ribotide synthase. ATP binding. metal ion binding. phosphoribosylamine-glycine ligase activity. phosphoribosylformylglycinamidine cyclo-ligase activity.
View unredacted entry
bifunctional aminoimidazole ribotide synthase/glycinamide ribotide synthase. ATP binding. metal ion binding. phosphoribosylamine-glycine ligase activity. phosphoribosylformylglycinamidine cyclo-ligase activity.
Solver output
ADE57 encodes a bifunctional enzyme catalyzing two early steps of de novo purine biosynthesis: glycinamide ribotide (GAR) synthase (step 2) and aminoimidazole ribotide (AIR) synthase (step 5). Adequate purine nucleotide pools are essential for DNA replication, repair, and RNA synthesis; deficiency in de novo purine synthesis forces cells to rely on salvage pathways and can trigger nucleotide imbalance, replication stress, and genomic instability. In yeast, purine biosynthesis is tightly coupled to one-carbon metabolism and TORC1-regulated anabolic programs; sufficient AMP/ATP levels support AMPK (Snf1) signaling and proper nutrient sensing. Loss of de novo purine synthesis capacity has been linked to reduced fitness and shortened chronological lifespan in yeast under nutrient-limiting conditions. Thus, the normal function of ADE57 in sustaining purine nucleotide pools supports cellular homeostasis and is expected to be pro-longevity.
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 that ADE57 supports cellular homeostasis and is therefore pro-longevity is plausible on the surface but incorrect. In yeast, many biosynthetic/anabolic genes (including purine biosynthesis genes) are anti-longevity because their deletion can extend lifespan by reducing anabolic activity and mimicking caloric restriction or nutrient limitation effects. The model acknowledged TORC1-regulated anabolic programs but then incorrectly concluded the gene is pro-longevity. The mechanistic reasoning about nucleotide pool homeostasis supporting longevity is not supported by the actual experimental data. The model had moderate confidence (0.62) but still got the direction wrong.
Raw API responses
solver
{
"reasoning": "ADE57 encodes a bifunctional enzyme catalyzing two early steps of de novo purine biosynthesis: glycinamide ribotide (GAR) synthase (step 2) and aminoimidazole ribotide (AIR) synthase (step 5). Adequate purine nucleotide pools are essential for DNA replication, repair, and RNA synthesis; deficiency in de novo purine synthesis forces cells to rely on salvage pathways and can trigger nucleotide imbalance, replication stress, and genomic instability. In yeast, purine biosynthesis is tightly coupled to one-carbon metabolism and TORC1-regulated anabolic programs; sufficient AMP/ATP levels support AMPK (Snf1) signaling and proper nutrient sensing. Loss of de novo purine synthesis capacity has been linked to reduced fitness and shortened chronological lifespan in yeast under nutrient-limiting conditions. Thus, the normal function of ADE57 in sustaining purine nucleotide pools supports cellular homeostasis and is expected to be pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"de novo purine biosynthesis",
"nucleotide pool homeostasis / AMPK-TORC1 nutrient sensing",
"one-carbon metabolism"
],
"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 that ADE57 supports cellular homeostasis and is therefore pro-longevity is plausible on the surface but incorrect. In yeast, many biosynthetic/anabolic genes (including purine biosynthesis genes) are anti-longevity because their deletion can extend lifespan by reducing anabolic activity and mimicking caloric restriction or nutrient limitation effects. The model acknowledged TORC1-regulated anabolic programs but then incorrectly concluded the gene is pro-longevity. The mechanistic reasoning about nucleotide pool homeostasis supporting longevity is not supported by the actual experimental data. The model had moderate confidence (0.62) but still got the direction wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}