AAT2
S. cerevisiae
aspartate transaminase AAT2
What the model saw
Gene: AAT2 Organism: Saccharomyces cerevisiae Known functions: aspartate transaminase AAT2. L-aspartate:2-oxoglutarate transaminase activity. catalytic activity. pyridoxal phosphate binding. ribosomal large subunit binding. transaminase activity.
View unredacted entry
aspartate transaminase AAT2. L-aspartate:2-oxoglutarate transaminase activity. catalytic activity. pyridoxal phosphate binding. ribosomal large subunit binding. transaminase activity.
Solver output
AAT2 encodes the cytoplasmic aspartate aminotransferase, which catalyzes the reversible transamination between oxaloacetate and glutamate to produce aspartate and 2-oxoglutarate (alpha-ketoglutarate). This reaction sits at a critical node connecting the TCA cycle, amino acid metabolism, and the malate-aspartate shuttle. By producing alpha-ketoglutarate, AAT2 feeds into TOR-sensitive metabolic pathways; alpha-ketoglutarate is a known pro-longevity metabolite that inhibits ATP synthase and TOR signaling in multiple organisms. Additionally, proper aspartate biosynthesis supports nucleotide synthesis and redox balance (NAD+/NADH), both of which are important for maintaining cellular homeostasis during aging. The pyridoxal phosphate (PLP)-dependent transamination activity and ribosomal large subunit binding suggest roles in coordinating translation with metabolic status. Loss of AAT2 in yeast has been associated with reduced chronological and replicative 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 correctly predicted pro_longevity for AAT2 in S. cerevisiae. The mechanistic reasoning is largely sound - AAT2 produces alpha-ketoglutarate which is a known pro-longevity metabolite, and the connection to TCA cycle, amino acid metabolism, and redox balance is reasonable. The model also correctly notes that loss of AAT2 is associated with reduced lifespan. The mechanism class of "deregulated_nutrient_sensing" is somewhat indirect but defensible given the alpha-ketoglutarate/TOR connection. The reasoning about ribosomal large subunit binding coordinating translation with metabolic status is speculative but not incorrect. Confidence of 0.62 is appropriately calibrated. Overall a well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "AAT2 encodes the cytoplasmic aspartate aminotransferase, which catalyzes the reversible transamination between oxaloacetate and glutamate to produce aspartate and 2-oxoglutarate (alpha-ketoglutarate). This reaction sits at a critical node connecting the TCA cycle, amino acid metabolism, and the malate-aspartate shuttle. By producing alpha-ketoglutarate, AAT2 feeds into TOR-sensitive metabolic pathways; alpha-ketoglutarate is a known pro-longevity metabolite that inhibits ATP synthase and TOR signaling in multiple organisms. Additionally, proper aspartate biosynthesis supports nucleotide synthesis and redox balance (NAD+/NADH), both of which are important for maintaining cellular homeostasis during aging. The pyridoxal phosphate (PLP)-dependent transamination activity and ribosomal large subunit binding suggest roles in coordinating translation with metabolic status. Loss of AAT2 in yeast has been associated with reduced chronological and replicative lifespan, consistent with a pro-longevity role.",
"confidence": 0.62,
"key_pathways": [
"alpha-ketoglutarate / TCA cycle metabolism",
"amino acid biosynthesis and nitrogen sensing",
"TOR signaling nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for AAT2 in S. cerevisiae. The mechanistic reasoning is largely sound - AAT2 produces alpha-ketoglutarate which is a known pro-longevity metabolite, and the connection to TCA cycle, amino acid metabolism, and redox balance is reasonable. The model also correctly notes that loss of AAT2 is associated with reduced lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is somewhat indirect but defensible given the alpha-ketoglutarate/TOR connection. The reasoning about ribosomal large subunit binding coordinating translation with metabolic status is speculative but not incorrect. Confidence of 0.62 is appropriately calibrated. Overall a well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}