ADE3

S. cerevisiae

trifunctional formate-tetrahydrofolate ligase/methenyltetrahydrofolate cyclohydrolase/methylenetetrahydrofolate dehydrogenase ADE3

What the model saw

Gene: ADE3
Organism: Saccharomyces cerevisiae
Known functions: trifunctional formate-tetrahydrofolate ligase/methenyltetrahydrofolate cyclohydrolase/methylenetetrahydrofolate dehydrogenase ADE3. ATP binding. catalytic activity. formate-tetrahydrofolate ligase activity. methenyltetrahydrofolate cyclohydrolase activity. methylenetetrahydrofolate dehydrogenase (NADP+) activity.

View unredacted entry

trifunctional formate-tetrahydrofolate ligase/methenyltetrahydrofolate cyclohydrolase/methylenetetrahydrofolate dehydrogenase ADE3. ATP binding. catalytic activity. formate-tetrahydrofolate ligase activity. methenyltetrahydrofolate cyclohydrolase activity. methylenetetrahydrofolate dehydrogenase (NADP+) activity.

Solver output

Predicted influence

Pro-longevity

Confidence

72%

Mechanism

Epigenetic alterations

Reasoning

ADE3 encodes a trifunctional enzyme central to one-carbon (folate) metabolism, catalyzing three sequential reactions: formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase (NADP+). These reactions interconvert folate one-carbon units that feed into purine biosynthesis (de novo AMP/GMP synthesis), thymidylate synthesis, and methionine/SAM regeneration. SAM is the universal methyl donor for DNA and histone methylation, directly linking one-carbon flux to epigenetic regulation. Loss of ADE3 function impairs folate-mediated one-carbon cycling, reducing SAM availability and disrupting methylation-dependent epigenetic maintenance, which is a recognized driver of aging. Additionally, adequate purine nucleotide pools supported by ADE3 are required for genome integrity and NAD+ metabolism. Thus, ADE3's normal function sustains epigenetic homeostasis and nucleotide sufficiency, both of which are pro-longevity.

Key pathways

one-carbon folate metabolism / SAM-dependent methylationde novo purine biosynthesisthymidylate synthesis and genome integrity

Longevity influence

Anti-longevity

Lifespan effect

Increase and Decrease

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. ADE3 is an anti-longevity gene in yeast, meaning its deletion or loss of function extends lifespan rather than shortening it. The model's reasoning is plausible on the surface (one-carbon metabolism, SAM, epigenetics) but leads to the wrong conclusion. The model assumed that because ADE3 supports important metabolic functions, it must be pro-longevity, but in reality ADE3 activity limits lifespan. The mechanism class of "epigenetic_alterations" is speculative and not well-supported for this gene specifically. The model failed to consider that ADE3 activity might promote aging through nucleotide/metabolic signaling that accelerates growth and aging, consistent with the anti-longevity classification.

Raw API responses

solver

{
  "reasoning": "ADE3 encodes a trifunctional enzyme central to one-carbon (folate) metabolism, catalyzing three sequential reactions: formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase (NADP+). These reactions interconvert folate one-carbon units that feed into purine biosynthesis (de novo AMP/GMP synthesis), thymidylate synthesis, and methionine/SAM regeneration. SAM is the universal methyl donor for DNA and histone methylation, directly linking one-carbon flux to epigenetic regulation. Loss of ADE3 function impairs folate-mediated one-carbon cycling, reducing SAM availability and disrupting methylation-dependent epigenetic maintenance, which is a recognized driver of aging. Additionally, adequate purine nucleotide pools supported by ADE3 are required for genome integrity and NAD+ metabolism. Thus, ADE3's normal function sustains epigenetic homeostasis and nucleotide sufficiency, both of which are pro-longevity.",
  "confidence": 0.72,
  "key_pathways": [
    "one-carbon folate metabolism / SAM-dependent methylation",
    "de novo purine biosynthesis",
    "thymidylate synthesis and genome integrity"
  ],
  "mechanism_class": "epigenetic_alterations",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. ADE3 is an anti-longevity gene in yeast, meaning its deletion or loss of function extends lifespan rather than shortening it. The model's reasoning is plausible on the surface (one-carbon metabolism, SAM, epigenetics) but leads to the wrong conclusion. The model assumed that because ADE3 supports important metabolic functions, it must be pro-longevity, but in reality ADE3 activity limits lifespan. The mechanism class of \"epigenetic_alterations\" is speculative and not well-supported for this gene specifically. The model failed to consider that ADE3 activity might promote aging through nucleotide/metabolic signaling that accelerates growth and aging, consistent with the anti-longevity classification.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}