LAT1
S. cerevisiae
dihydrolipoyllysine-residue acetyltransferase
What the model saw
Gene: LAT1 Organism: Saccharomyces cerevisiae Known functions: dihydrolipoyllysine-residue acetyltransferase. acyltransferase activity. dihydrolipoyllysine-residue acetyltransferase activity.
View unredacted entry
dihydrolipoyllysine-residue acetyltransferase. acyltransferase activity. dihydrolipoyllysine-residue acetyltransferase activity.
Solver output
LAT1 encodes the dihydrolipoyllysine-residue acetyltransferase (E2) subunit of the pyruvate dehydrogenase complex (PDC) in S. cerevisiae. This enzyme catalyzes the transfer of the acetyl group from lipoamide to CoA, producing acetyl-CoA, which is the central metabolite linking glycolysis to the TCA cycle and mitochondrial respiration. Proper PDC function is essential for mitochondrial energy metabolism; loss of LAT1 impairs acetyl-CoA production, disrupts TCA cycle flux, and compromises mitochondrial function. Mitochondrial dysfunction is a well-established hallmark of aging, and maintaining robust PDC activity supports healthy mitochondrial respiration and metabolic homeostasis, which is generally associated with extended lifespan in yeast. Additionally, acetyl-CoA availability influences histone acetylation and thus epigenetic regulation, further linking LAT1 activity to longevity-relevant pathways.
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 LAT1 in S. cerevisiae. The mechanistic reasoning is sound: LAT1 encodes the E2 subunit of the pyruvate dehydrogenase complex, which is critical for acetyl-CoA production and mitochondrial energy metabolism. The model correctly identifies that loss of LAT1 would impair mitochondrial function, a hallmark of aging. The additional mention of acetyl-CoA's role in epigenetic regulation is a reasonable secondary pathway. The confidence of 0.62 is appropriately moderate. The reasoning is well-grounded in yeast biology, though the model could have been more specific about actual experimental evidence (e.g., deletion studies showing reduced lifespan). Overall, a solid prediction with correct answer and plausible mechanism.
Raw API responses
solver
{
"reasoning": "LAT1 encodes the dihydrolipoyllysine-residue acetyltransferase (E2) subunit of the pyruvate dehydrogenase complex (PDC) in S. cerevisiae. This enzyme catalyzes the transfer of the acetyl group from lipoamide to CoA, producing acetyl-CoA, which is the central metabolite linking glycolysis to the TCA cycle and mitochondrial respiration. Proper PDC function is essential for mitochondrial energy metabolism; loss of LAT1 impairs acetyl-CoA production, disrupts TCA cycle flux, and compromises mitochondrial function. Mitochondrial dysfunction is a well-established hallmark of aging, and maintaining robust PDC activity supports healthy mitochondrial respiration and metabolic homeostasis, which is generally associated with extended lifespan in yeast. Additionally, acetyl-CoA availability influences histone acetylation and thus epigenetic regulation, further linking LAT1 activity to longevity-relevant pathways.",
"confidence": 0.62,
"key_pathways": [
"pyruvate dehydrogenase complex (PDC) / acetyl-CoA production",
"TCA cycle / mitochondrial respiration",
"acetyl-CoA-dependent epigenetic regulation"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for LAT1 in S. cerevisiae. The mechanistic reasoning is sound: LAT1 encodes the E2 subunit of the pyruvate dehydrogenase complex, which is critical for acetyl-CoA production and mitochondrial energy metabolism. The model correctly identifies that loss of LAT1 would impair mitochondrial function, a hallmark of aging. The additional mention of acetyl-CoA's role in epigenetic regulation is a reasonable secondary pathway. The confidence of 0.62 is appropriately moderate. The reasoning is well-grounded in yeast biology, though the model could have been more specific about actual experimental evidence (e.g., deletion studies showing reduced lifespan). Overall, a solid prediction with correct answer and plausible mechanism.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}