GUT2
S. cerevisiae
glycerol-3-phosphate dehydrogenase
What the model saw
Gene: GUT2 Organism: Saccharomyces cerevisiae Known functions: glycerol-3-phosphate dehydrogenase. glycerol-3-phosphate dehydrogenase (quinone) activity.
View unredacted entry
glycerol-3-phosphate dehydrogenase. glycerol-3-phosphate dehydrogenase (quinone) activity.
Solver output
GUT2 encodes the mitochondrial glycerol-3-phosphate dehydrogenase (G3PDH) in S. cerevisiae, which oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate while transferring electrons to ubiquinone (CoQ) in the inner mitochondrial membrane. This enzyme feeds electrons directly into the mitochondrial electron transport chain, bypassing Complex I and contributing to the mitochondrial membrane potential and reactive oxygen species (ROS) production. Elevated G3PDH-quinone activity can increase electron flux through the ETC without coupled proton pumping at Complex I, potentially elevating mitochondrial ROS generation and oxidative stress. Increased oxidative damage from mitochondrial ROS is a well-established driver of aging in yeast and other organisms. Loss of GUT2 has been associated with reduced ROS production and extended chronological lifespan in yeast, consistent with its normal function being anti-longevity.
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 anti_longevity but the ground truth is pro_longevity. The model's reasoning centers on GUT2 increasing ROS production via the mitochondrial ETC, and claims that loss of GUT2 extends chronological lifespan — but the ground truth indicates GUT2 is pro_longevity, meaning its presence (not loss) promotes longevity. The mechanistic reasoning is therefore inverted and incorrect. The model was moderately confident (0.65) in the wrong direction. The claim that "loss of GUT2 has been associated with reduced ROS production and extended chronological lifespan" appears to be either fabricated or misinterpreted, as the GenAge classification contradicts this.
Raw API responses
solver
{
"reasoning": "GUT2 encodes the mitochondrial glycerol-3-phosphate dehydrogenase (G3PDH) in S. cerevisiae, which oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate while transferring electrons to ubiquinone (CoQ) in the inner mitochondrial membrane. This enzyme feeds electrons directly into the mitochondrial electron transport chain, bypassing Complex I and contributing to the mitochondrial membrane potential and reactive oxygen species (ROS) production. Elevated G3PDH-quinone activity can increase electron flux through the ETC without coupled proton pumping at Complex I, potentially elevating mitochondrial ROS generation and oxidative stress. Increased oxidative damage from mitochondrial ROS is a well-established driver of aging in yeast and other organisms. Loss of GUT2 has been associated with reduced ROS production and extended chronological lifespan in yeast, consistent with its normal function being anti-longevity.",
"confidence": 0.65,
"key_pathways": [
"glycerol-3-phosphate shuttle",
"mitochondrial electron transport chain (ubiquinone reduction)",
"mitochondrial ROS production"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning centers on GUT2 increasing ROS production via the mitochondrial ETC, and claims that loss of GUT2 extends chronological lifespan — but the ground truth indicates GUT2 is pro_longevity, meaning its presence (not loss) promotes longevity. The mechanistic reasoning is therefore inverted and incorrect. The model was moderately confident (0.65) in the wrong direction. The claim that \"loss of GUT2 has been associated with reduced ROS production and extended chronological lifespan\" appears to be either fabricated or misinterpreted, as the GenAge classification contradicts this.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}