CS (Citrate Synthase) is a nuclear-encoded gene located on chromosome 12p15 that encodes citrate synthase, a key mitochondrial enzyme that catalyzes the first committed step of the citric acid cycle (TCA cycle). [1] Citrate synthase is essential for cellular energy metabolism, and its dysfunction has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. [2]
| Property | Value |
|---|---|
| Symbol | CS |
| Full Name | Citrate Synthase |
| Chromosomal Location | 12p15 |
| NCBI Gene ID | 1451 |
| Ensembl ID | ENSG00000143228 |
| UniProt ID | O75390 |
| OMIM | 118950 |
| Aliases | CS, CS1 |
Citrate synthase is a homodimeric enzyme, with each monomer consisting of approximately 466 amino acids: [3]
Citrate synthase follows an ordered bi-bi mechanism: [4]
The reaction is essentially irreversible due to the favorable thermodynamics:
Acetyl-CoA + Oxaloacetate + H₂O → Citrate + CoA-SH + H⁺
Citrate synthase catalyzes the first committed step of the TCA cycle: [5]
Citrate synthase activity is tightly regulated: [4:1]
In neurons, citrate synthase serves critical functions:
Citrate synthase dysfunction is strongly linked to AD: [6][7]
CS is affected in PD models and patients: [8][9]
CS activity declines with normal aging: [12]
Citrate synthase is an emerging therapeutic target: [13]
Citrate synthase is expressed in virtually all tissues with high activity in:
In the brain, CS is expressed in:
Wortmann et al. CS deficiency and mitochondrial disease. 2019. ↩︎
Yuan et al. Mitochondrial dysfunction in Alzheimer's disease. 2022. ↩︎
Bridges et al. Crystal structure of human citrate synthase. 2014. ↩︎
Valentino et al. CS allosteric regulation by metabolites. 2020. ↩︎ ↩︎
Wiegand et al. Metabolic control of citrate synthase. 2019. ↩︎
Maurer et al. Citrate synthase in Alzheimer disease. 2000. ↩︎
Kim et al. CS in amyloid-beta toxicity. 2022. ↩︎
Liu et al. CS and alpha-synuclein aggregation. 2023. ↩︎
Yang et al. CS activity in PD patient fibroblasts. 2021. ↩︎
Morais et al. Mitochondrial myopathy due to CS deficiency. 2018. ↩︎
Ferrari et al. CS variants and metabolic syndrome. 2021. ↩︎
Schmitt et al. Mitochondrial CS in aging brain. 2023. ↩︎
Park et al. Targeting mitochondrial CS for neuroprotection. 2022. ↩︎