AAH1
S. cerevisiae
adenine deaminase
What the model saw
Gene: AAH1 Organism: Saccharomyces cerevisiae Known functions: adenine deaminase. adenine deaminase activity. deaminase activity. protein binding. zinc ion binding.
View unredacted entry
adenine deaminase. adenine deaminase activity. deaminase activity. protein binding. zinc ion binding.
Solver output
AAH1 encodes adenine deaminase in S. cerevisiae, which catalyzes the hydrolytic deamination of adenine to hypoxanthine in the purine salvage pathway. By consuming adenine and channeling it toward hypoxanthine/IMP, AAH1 activity reduces the cellular adenine pool. Reduced adenine availability can lower NAD+ precursor flux and diminish the adenylate energy charge, both of which are linked to nutrient sensing and metabolic homeostasis. Importantly, adenine limitation in yeast is associated with reduced TORC1 signaling and can paradoxically extend lifespan, suggesting that AAH1-mediated depletion of adenine could be either beneficial or detrimental depending on context; however, excessive catabolism of adenine can deplete purine pools needed for NAD+ synthesis and ATP production, potentially impairing mitochondrial function and energy sensing. The zinc-dependent deaminase activity places this enzyme in a metabolic regulatory node where its normal function (consuming adenine) would tend to reduce adenine availability, which in excess could compromise cellular energy status and nutrient sensing pathways, thus opposing 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 correctly predicted "anti_longevity" for AAH1, matching the ground truth. However, the mechanistic reasoning is speculative and convoluted. The model constructs an indirect chain: AAH1 depletes adenine → reduces NAD+ precursor flux → impairs energy sensing → opposes longevity. This is not the established mechanism. In yeast, AAH1 deletion studies show that loss of adenine deaminase extends lifespan, suggesting AAH1 normally promotes aging (anti-longevity). The actual mechanism is more directly related to purine metabolism and its effects on cellular aging, not specifically through TORC1 nutrient sensing as the primary pathway. The model hedges significantly ("either beneficial or detrimental depending on context") and arrives at the correct answer somewhat tentatively (0.52 confidence). The reasoning is largely speculative and not grounded in well-established experimental evidence about AAH1's specific role in yeast aging.
Raw API responses
solver
{
"reasoning": "AAH1 encodes adenine deaminase in S. cerevisiae, which catalyzes the hydrolytic deamination of adenine to hypoxanthine in the purine salvage pathway. By consuming adenine and channeling it toward hypoxanthine/IMP, AAH1 activity reduces the cellular adenine pool. Reduced adenine availability can lower NAD+ precursor flux and diminish the adenylate energy charge, both of which are linked to nutrient sensing and metabolic homeostasis. Importantly, adenine limitation in yeast is associated with reduced TORC1 signaling and can paradoxically extend lifespan, suggesting that AAH1-mediated depletion of adenine could be either beneficial or detrimental depending on context; however, excessive catabolism of adenine can deplete purine pools needed for NAD+ synthesis and ATP production, potentially impairing mitochondrial function and energy sensing. The zinc-dependent deaminase activity places this enzyme in a metabolic regulatory node where its normal function (consuming adenine) would tend to reduce adenine availability, which in excess could compromise cellular energy status and nutrient sensing pathways, thus opposing longevity.",
"confidence": 0.52,
"key_pathways": [
"purine salvage pathway",
"adenylate/NAD+ biosynthesis",
"TORC1 nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted \"anti_longevity\" for AAH1, matching the ground truth. However, the mechanistic reasoning is speculative and convoluted. The model constructs an indirect chain: AAH1 depletes adenine → reduces NAD+ precursor flux → impairs energy sensing → opposes longevity. This is not the established mechanism. In yeast, AAH1 deletion studies show that loss of adenine deaminase extends lifespan, suggesting AAH1 normally promotes aging (anti-longevity). The actual mechanism is more directly related to purine metabolism and its effects on cellular aging, not specifically through TORC1 nutrient sensing as the primary pathway. The model hedges significantly (\"either beneficial or detrimental depending on context\") and arrives at the correct answer somewhat tentatively (0.52 confidence). The reasoning is largely speculative and not grounded in well-established experimental evidence about AAH1's specific role in yeast aging.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}