cth-1
C. elegans
cystathionine gamma-lyase
What the model saw
Gene: cth-1 Organism: Caenorhabditis elegans Known functions: cystathionine gamma-lyase. cystathionine gamma-lyase activity. pyridoxal phosphate binding.
View unredacted entry
cystathionine gamma-lyase. cystathionine gamma-lyase activity. pyridoxal phosphate binding.
Solver output
Cystathionine gamma-lyase (CTH) is the terminal enzyme in the transsulfuration pathway, catalyzing the conversion of cystathionine to cysteine, alpha-ketobutyrate, and hydrogen sulfide (H2S). H2S is a gasotransmitter with well-established cytoprotective and anti-aging effects: it activates stress-response pathways (including DAF-16/FOXO and Nrf2/SKN-1), reduces oxidative damage, and has been shown to extend lifespan in C. elegans and other model organisms. The pyridoxal phosphate (PLP) cofactor binding is consistent with canonical transsulfuration enzyme activity. Increased transsulfuration flux elevates cysteine availability for glutathione biosynthesis, further bolstering antioxidant defenses. Loss of cth-1 function in C. elegans has been associated with reduced H2S production and shortened lifespan, supporting a pro-longevity role for this gene.
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 pro_longevity for cth-1 in C. elegans. The mechanistic reasoning is well-grounded: cystathionine gamma-lyase produces H2S via the transsulfuration pathway, H2S has cytoprotective effects, and loss of cth-1 reduces H2S and shortens lifespan. The model also correctly identifies downstream pathways (glutathione biosynthesis, DAF-16/FOXO, SKN-1/Nrf2). The reasoning is biologically sound and consistent with published literature. Confidence of 0.72 is appropriate given the specificity of the claim. Minor deduction: the claim that "loss of cth-1 function in C. elegans has been associated with reduced H2S production and shortened lifespan" is stated with some confidence but may be partially inferred rather than directly cited from literature, though it is plausible.
Raw API responses
solver
{
"reasoning": "Cystathionine gamma-lyase (CTH) is the terminal enzyme in the transsulfuration pathway, catalyzing the conversion of cystathionine to cysteine, alpha-ketobutyrate, and hydrogen sulfide (H2S). H2S is a gasotransmitter with well-established cytoprotective and anti-aging effects: it activates stress-response pathways (including DAF-16/FOXO and Nrf2/SKN-1), reduces oxidative damage, and has been shown to extend lifespan in C. elegans and other model organisms. The pyridoxal phosphate (PLP) cofactor binding is consistent with canonical transsulfuration enzyme activity. Increased transsulfuration flux elevates cysteine availability for glutathione biosynthesis, further bolstering antioxidant defenses. Loss of cth-1 function in C. elegans has been associated with reduced H2S production and shortened lifespan, supporting a pro-longevity role for this gene.",
"confidence": 0.72,
"key_pathways": [
"transsulfuration pathway / hydrogen sulfide production",
"glutathione biosynthesis / antioxidant defense",
"DAF-16/FOXO and SKN-1/Nrf2 stress response"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for cth-1 in C. elegans. The mechanistic reasoning is well-grounded: cystathionine gamma-lyase produces H2S via the transsulfuration pathway, H2S has cytoprotective effects, and loss of cth-1 reduces H2S and shortens lifespan. The model also correctly identifies downstream pathways (glutathione biosynthesis, DAF-16/FOXO, SKN-1/Nrf2). The reasoning is biologically sound and consistent with published literature. Confidence of 0.72 is appropriate given the specificity of the claim. Minor deduction: the claim that \"loss of cth-1 function in C. elegans has been associated with reduced H2S production and shortened lifespan\" is stated with some confidence but may be partially inferred rather than directly cited from literature, though it is plausible.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}