aca1
S. pombe
L-azetidine-2-carboxylic acid acetyltransferase Aca1
What the model saw
Gene: aca1 Organism: Schizosaccharomyces pombe Known functions: L-azetidine-2-carboxylic acid acetyltransferase Aca1. acyltransferase activity, transferring groups other than amino-acyl groups. azetidine-2-carboxylic acid acetyltransferase activity.
View unredacted entry
L-azetidine-2-carboxylic acid acetyltransferase Aca1. acyltransferase activity, transferring groups other than amino-acyl groups. azetidine-2-carboxylic acid acetyltransferase activity.
Solver output
Aca1 is an L-azetidine-2-carboxylic acid (AZC) acetyltransferase that detoxifies AZC, a toxic proline analog, by acetylating it. AZC is a well-established proteotoxic stressor: when misincorporated into proteins in place of proline, it causes widespread protein misfolding and aggregation. By neutralizing AZC before it can be incorporated into nascent polypeptides, Aca1 protects proteostasis and prevents the accumulation of misfolded proteins. Maintenance of proteostasis is a canonical pro-longevity mechanism, as loss of proteostasis is a hallmark of aging. Thus, the normal function of Aca1 opposes proteotoxic stress and is expected to be pro-longevity. The confidence is moderate because AZC is an exogenous compound and the endogenous substrate/physiological relevance in the absence of AZC exposure is less certain.
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 about AZC detoxification and proteostasis maintenance is biochemically plausible and internally consistent, but leads to the wrong conclusion. The model correctly identifies Aca1 as an AZC acetyltransferase but incorrectly infers that detoxifying a proteotoxic stressor would be pro-longevity. In reality, aca1 is anti-longevity in S. pombe, suggesting that either the gene's deletion extends lifespan or its overexpression shortens it. The model's mechanistic reasoning about AZC detoxification being protective is reasonable in principle, but the actual experimental data shows the opposite effect on longevity. The model did note some uncertainty about the physiological relevance in the absence of exogenous AZC, which is a valid caveat, but still committed to the wrong answer with moderate confidence (0.62).
Raw API responses
solver
{
"reasoning": "Aca1 is an L-azetidine-2-carboxylic acid (AZC) acetyltransferase that detoxifies AZC, a toxic proline analog, by acetylating it. AZC is a well-established proteotoxic stressor: when misincorporated into proteins in place of proline, it causes widespread protein misfolding and aggregation. By neutralizing AZC before it can be incorporated into nascent polypeptides, Aca1 protects proteostasis and prevents the accumulation of misfolded proteins. Maintenance of proteostasis is a canonical pro-longevity mechanism, as loss of proteostasis is a hallmark of aging. Thus, the normal function of Aca1 opposes proteotoxic stress and is expected to be pro-longevity. The confidence is moderate because AZC is an exogenous compound and the endogenous substrate/physiological relevance in the absence of AZC exposure is less certain.",
"confidence": 0.62,
"key_pathways": [
"AZC detoxification / proteotoxic stress defense",
"proteostasis maintenance",
"acyltransferase-mediated xenobiotic/analog neutralization"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about AZC detoxification and proteostasis maintenance is biochemically plausible and internally consistent, but leads to the wrong conclusion. The model correctly identifies Aca1 as an AZC acetyltransferase but incorrectly infers that detoxifying a proteotoxic stressor would be pro-longevity. In reality, aca1 is anti-longevity in S. pombe, suggesting that either the gene's deletion extends lifespan or its overexpression shortens it. The model's mechanistic reasoning about AZC detoxification being protective is reasonable in principle, but the actual experimental data shows the opposite effect on longevity. The model did note some uncertainty about the physiological relevance in the absence of exogenous AZC, which is a valid caveat, but still committed to the wrong answer with moderate confidence (0.62).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}