gdh-1

C. elegans

Glutamate dehydrogenase

What the model saw

Gene: gdh-1
Organism: Caenorhabditis elegans
Known functions: Glutamate dehydrogenase. L-glutamate dehydrogenase (NAD+) activity. L-glutamate dehydrogenase [NAD(P)+] activity. oxidoreductase activity. oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor.

View unredacted entry

Glutamate dehydrogenase. L-glutamate dehydrogenase (NAD+) activity. L-glutamate dehydrogenase [NAD(P)+] activity. oxidoreductase activity. oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor.

Solver output

Predicted influence

Pro-longevity

Confidence

62%

Mechanism

Deregulated nutrient sensing

Reasoning

Glutamate dehydrogenase (GDH) catalyzes the reversible oxidative deamination of L-glutamate to α-ketoglutarate (α-KG) using NAD(P)+ as a cofactor. α-KG is a key TCA cycle intermediate and a well-established pro-longevity metabolite in C. elegans, shown to extend lifespan by inhibiting ATP synthase and TOR signaling. Additionally, GDH activity generates NADH/NADPH, influencing cellular redox balance and mitochondrial metabolism. The reaction also links amino acid catabolism to the TCA cycle, connecting nutrient sensing (particularly nitrogen/amino acid status) to energy metabolism. In C. elegans, gdh-1 loss has been associated with reduced α-KG production and shortened lifespan, consistent with a pro-longevity role for the enzyme. The NAD(P)+ dependence further ties this enzyme to the broader NAD+ metabolism network, which is central to sirtuin-mediated longevity pathways.

Key pathways

alpha-ketoglutarate / TCA cycle metabolismTOR nutrient sensing pathwayNAD+/NADH redox balance

Longevity influence

Anti-longevity

Lifespan effect

Increase

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 but the ground truth is anti_longevity. The model's reasoning is plausible on the surface (α-KG as a pro-longevity metabolite, NAD+ metabolism), but it appears to have fabricated or misremembered the specific C. elegans experimental evidence, claiming "gdh-1 loss has been associated with reduced α-KG production and shortened lifespan" — which would support pro_longevity. In reality, gdh-1 is anti_longevity, meaning its loss likely extends lifespan. The model constructed a coherent-sounding but incorrect mechanistic narrative and reached the wrong conclusion with moderate confidence (0.62).

Raw API responses

solver

{
  "reasoning": "Glutamate dehydrogenase (GDH) catalyzes the reversible oxidative deamination of L-glutamate to α-ketoglutarate (α-KG) using NAD(P)+ as a cofactor. α-KG is a key TCA cycle intermediate and a well-established pro-longevity metabolite in C. elegans, shown to extend lifespan by inhibiting ATP synthase and TOR signaling. Additionally, GDH activity generates NADH/NADPH, influencing cellular redox balance and mitochondrial metabolism. The reaction also links amino acid catabolism to the TCA cycle, connecting nutrient sensing (particularly nitrogen/amino acid status) to energy metabolism. In C. elegans, gdh-1 loss has been associated with reduced α-KG production and shortened lifespan, consistent with a pro-longevity role for the enzyme. The NAD(P)+ dependence further ties this enzyme to the broader NAD+ metabolism network, which is central to sirtuin-mediated longevity pathways.",
  "confidence": 0.62,
  "key_pathways": [
    "alpha-ketoglutarate / TCA cycle metabolism",
    "TOR nutrient sensing pathway",
    "NAD+/NADH redox balance"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface (α-KG as a pro-longevity metabolite, NAD+ metabolism), but it appears to have fabricated or misremembered the specific C. elegans experimental evidence, claiming \"gdh-1 loss has been associated with reduced α-KG production and shortened lifespan\" — which would support pro_longevity. In reality, gdh-1 is anti_longevity, meaning its loss likely extends lifespan. The model constructed a coherent-sounding but incorrect mechanistic narrative and reached the wrong conclusion with moderate confidence (0.62).",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}