SAM1
S. cerevisiae
methionine adenosyltransferase SAM1
What the model saw
Gene: SAM1 Organism: Saccharomyces cerevisiae Known functions: methionine adenosyltransferase SAM1. ATP binding. methionine adenosyltransferase activity. protein binding.
View unredacted entry
methionine adenosyltransferase SAM1. ATP binding. methionine adenosyltransferase activity. protein binding.
Solver output
SAM1 encodes methionine adenosyltransferase, the enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM) from methionine and ATP. SAM is the universal methyl donor for methyltransferase reactions, including histone and DNA methylation. In yeast, elevated SAM levels drive increased histone H3K4 methylation via the COMPASS complex (Set1), which has been linked to shortened chronological and replicative lifespan. Caloric restriction and methionine restriction extend lifespan partly by reducing SAM availability and downstream methylation marks. Thus, higher SAM1 activity increases SAM pools, promoting pro-aging epigenetic states rather than the hypomethylation associated with longevity under nutrient restriction.
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 SAM1 as anti_longevity. The mechanistic reasoning is well-grounded: SAM1 encodes methionine adenosyltransferase which produces S-adenosylmethionine (SAM), the universal methyl donor. The connection to histone methylation via COMPASS/Set1 and the methionine restriction longevity pathway is scientifically sound. The model correctly identifies that elevated SAM levels promote pro-aging epigenetic states. The mechanism class of "epigenetic_alterations" is reasonable, though the primary mechanism could also be framed as metabolic (SAM biosynthesis). The reasoning is coherent and well-supported by known biology. Confidence of 0.72 is appropriate given the complexity of the pathway.
Raw API responses
solver
{
"reasoning": "SAM1 encodes methionine adenosyltransferase, the enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM) from methionine and ATP. SAM is the universal methyl donor for methyltransferase reactions, including histone and DNA methylation. In yeast, elevated SAM levels drive increased histone H3K4 methylation via the COMPASS complex (Set1), which has been linked to shortened chronological and replicative lifespan. Caloric restriction and methionine restriction extend lifespan partly by reducing SAM availability and downstream methylation marks. Thus, higher SAM1 activity increases SAM pools, promoting pro-aging epigenetic states rather than the hypomethylation associated with longevity under nutrient restriction.",
"confidence": 0.72,
"key_pathways": [
"S-adenosylmethionine biosynthesis",
"histone H3K4 methylation (COMPASS/Set1)",
"methionine restriction longevity pathway"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted SAM1 as anti_longevity. The mechanistic reasoning is well-grounded: SAM1 encodes methionine adenosyltransferase which produces S-adenosylmethionine (SAM), the universal methyl donor. The connection to histone methylation via COMPASS/Set1 and the methionine restriction longevity pathway is scientifically sound. The model correctly identifies that elevated SAM levels promote pro-aging epigenetic states. The mechanism class of \"epigenetic_alterations\" is reasonable, though the primary mechanism could also be framed as metabolic (SAM biosynthesis). The reasoning is coherent and well-supported by known biology. Confidence of 0.72 is appropriate given the complexity of the pathway.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}