Metabolic Checkpoint CPS1 Sustains TCA Anaplerosis via Urea Cycle in IDH-Mutant Gliomas - PubMed
4 hours ago
- #glioma
- #metabolism
- #CPS1
- IDH-mutant gliomas have a unique metabolism with high 2-HG and low α-ketoglutarate.
- Metabolomics reveals elevated urea cycle metabolites in IDH-mutant gliomas.
- CPS1, a urea cycle enzyme, acts as a checkpoint to maintain the TCA cycle via a half urea cycle.
- CPS1 upregulation drives fumarate production to sustain TCA flux in these tumors.
- Inhibiting CPS1 reduces fumarate, lowers 2-HG, impairs mitochondrial respiration, and suppresses tumor growth in models.
- Targeting CPS1 could be a promising metabolic therapy for IDH-mutant gliomas.