AAT1
S. cerevisiae
aspartate transaminase AAT1
What the model saw
Gene: AAT1 Organism: Saccharomyces cerevisiae Known functions: aspartate transaminase AAT1. L-aspartate:2-oxoglutarate transaminase activity. catalytic activity. pyridoxal phosphate binding. transaminase activity.
View unredacted entry
aspartate transaminase AAT1. L-aspartate:2-oxoglutarate transaminase activity. catalytic activity. pyridoxal phosphate binding. transaminase activity.
Solver output
AAT1 encodes the mitochondrial aspartate transaminase in S. cerevisiae, which catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and 2-oxoglutarate (alpha-ketoglutarate). This reaction is a central node in the malate-aspartate shuttle, connecting amino acid metabolism to the TCA cycle and mitochondrial redox balance. By producing alpha-ketoglutarate, AAT1 activity feeds into the TCA cycle and supports mitochondrial energy metabolism, which is associated with healthy aging. Additionally, alpha-ketoglutarate is a known pro-longevity metabolite that inhibits ATP synthase and activates AMPK-like signaling, and aspartate biosynthesis supports nucleotide synthesis and cellular homeostasis. Loss of mitochondrial aspartate transaminase activity impairs the malate-aspartate shuttle, disrupts NAD+/NADH balance, and compromises mitochondrial function—hallmarks associated with accelerated aging. Thus, the normal function of AAT1 is expected to support longevity through maintenance of mitochondrial metabolic integrity and nutrient sensing.
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 AAT1 in S. cerevisiae. The mechanistic reasoning is well-grounded: AAT1 encodes mitochondrial aspartate transaminase, and the model correctly identifies its role in the malate-aspartate shuttle, TCA cycle, NAD+/NADH balance, and alpha-ketoglutarate production as pro-longevity mechanisms. The alpha-ketoglutarate connection to longevity is a reasonable and scientifically supported claim. The mechanism class "deregulated_nutrient_sensing" is a somewhat loose fit — the primary mechanism is more about mitochondrial metabolic integrity than nutrient sensing per se — but the reasoning text itself is sound. Confidence of 0.62 is appropriately moderate. Overall a strong prediction with good mechanistic support.
Raw API responses
solver
{
"reasoning": "AAT1 encodes the mitochondrial aspartate transaminase in S. cerevisiae, which catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and 2-oxoglutarate (alpha-ketoglutarate). This reaction is a central node in the malate-aspartate shuttle, connecting amino acid metabolism to the TCA cycle and mitochondrial redox balance. By producing alpha-ketoglutarate, AAT1 activity feeds into the TCA cycle and supports mitochondrial energy metabolism, which is associated with healthy aging. Additionally, alpha-ketoglutarate is a known pro-longevity metabolite that inhibits ATP synthase and activates AMPK-like signaling, and aspartate biosynthesis supports nucleotide synthesis and cellular homeostasis. Loss of mitochondrial aspartate transaminase activity impairs the malate-aspartate shuttle, disrupts NAD+/NADH balance, and compromises mitochondrial function—hallmarks associated with accelerated aging. Thus, the normal function of AAT1 is expected to support longevity through maintenance of mitochondrial metabolic integrity and nutrient sensing.",
"confidence": 0.62,
"key_pathways": [
"malate-aspartate shuttle / TCA cycle",
"alpha-ketoglutarate metabolism and nutrient sensing",
"mitochondrial NAD+/NADH redox balance"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for AAT1 in S. cerevisiae. The mechanistic reasoning is well-grounded: AAT1 encodes mitochondrial aspartate transaminase, and the model correctly identifies its role in the malate-aspartate shuttle, TCA cycle, NAD+/NADH balance, and alpha-ketoglutarate production as pro-longevity mechanisms. The alpha-ketoglutarate connection to longevity is a reasonable and scientifically supported claim. The mechanism class \"deregulated_nutrient_sensing\" is a somewhat loose fit — the primary mechanism is more about mitochondrial metabolic integrity than nutrient sensing per se — but the reasoning text itself is sound. Confidence of 0.62 is appropriately moderate. Overall a strong prediction with good mechanistic support.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}