LYS9
S. cerevisiae
saccharopine dehydrogenase (NADP+, L-glutamate-forming)
What the model saw
Gene: LYS9 Organism: Saccharomyces cerevisiae Known functions: saccharopine dehydrogenase (NADP+, L-glutamate-forming). saccharopine dehydrogenase (NADP+, L-glutamate-forming) activity. saccharopine dehydrogenase activity.
View unredacted entry
saccharopine dehydrogenase (NADP+, L-glutamate-forming). saccharopine dehydrogenase (NADP+, L-glutamate-forming) activity. saccharopine dehydrogenase activity.
Solver output
LYS9 encodes saccharopine dehydrogenase, which catalyzes a key step in the α-aminoadipate pathway for lysine biosynthesis in yeast — specifically the NADP+-dependent oxidative cleavage of saccharopine to produce L-glutamate and α-aminoadipate-6-semialdehyde. Lysine is an essential amino acid whose intracellular availability feeds into amino acid sensing pathways (e.g., TORC1 via amino acid sufficiency signals). Adequate lysine biosynthesis supports proteostasis and proper protein synthesis. Loss of LYS9 would create lysine auxotrophy, impairing protein synthesis and potentially triggering chronic amino acid starvation stress, which could paradoxically mimic caloric restriction; however, in a wild-type context, functional LYS9 ensures sufficient lysine pools that support normal cellular metabolism and proteome integrity. The NADP+/NADPH balance modulated by this reaction also connects to redox homeostasis. On balance, a functional lysine biosynthesis pathway supports normal growth and metabolic health, placing LYS9 in a pro-longevity role through maintenance of nutrient sensing homeostasis.
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 is speculative and ultimately incorrect. It correctly identifies LYS9's role in lysine biosynthesis via the α-aminoadipate pathway, but then constructs a narrative that functional LYS9 supports longevity through nutrient sensing homeostasis. In reality, LYS9 is anti-longevity in yeast, meaning its deletion extends lifespan. The model briefly acknowledges that loss of LYS9 could mimic caloric restriction (which would actually point toward anti_longevity classification for the gene), but then dismisses this in favor of the pro_longevity conclusion. The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about TORC1 amino acid sensing and NADP+/NADPH balance is speculative and not well-supported for this specific gene.
Raw API responses
solver
{
"reasoning": "LYS9 encodes saccharopine dehydrogenase, which catalyzes a key step in the α-aminoadipate pathway for lysine biosynthesis in yeast — specifically the NADP+-dependent oxidative cleavage of saccharopine to produce L-glutamate and α-aminoadipate-6-semialdehyde. Lysine is an essential amino acid whose intracellular availability feeds into amino acid sensing pathways (e.g., TORC1 via amino acid sufficiency signals). Adequate lysine biosynthesis supports proteostasis and proper protein synthesis. Loss of LYS9 would create lysine auxotrophy, impairing protein synthesis and potentially triggering chronic amino acid starvation stress, which could paradoxically mimic caloric restriction; however, in a wild-type context, functional LYS9 ensures sufficient lysine pools that support normal cellular metabolism and proteome integrity. The NADP+/NADPH balance modulated by this reaction also connects to redox homeostasis. On balance, a functional lysine biosynthesis pathway supports normal growth and metabolic health, placing LYS9 in a pro-longevity role through maintenance of nutrient sensing homeostasis.",
"confidence": 0.62,
"key_pathways": [
"lysine biosynthesis (α-aminoadipate pathway)",
"TORC1 amino acid sensing",
"NADP+/NADPH redox balance"
],
"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 is speculative and ultimately incorrect. It correctly identifies LYS9's role in lysine biosynthesis via the α-aminoadipate pathway, but then constructs a narrative that functional LYS9 supports longevity through nutrient sensing homeostasis. In reality, LYS9 is anti-longevity in yeast, meaning its deletion extends lifespan. The model briefly acknowledges that loss of LYS9 could mimic caloric restriction (which would actually point toward anti_longevity classification for the gene), but then dismisses this in favor of the pro_longevity conclusion. The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about TORC1 amino acid sensing and NADP+/NADPH balance is speculative and not well-supported for this specific gene.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}