Cs Protein is involved in cellular processes relevant to neurodegeneration. For detailed information, refer to the References section.
Citrate synthase is a mitochondrial enzyme that catalyzes the first step of the TCA cycle, condensing acetyl-CoA with oxaloacetate to form citrate. It is a key metabolic enzyme essential for cellular energy production. [1]
| Protein Name | Citrate Synthase |
|---|---|
| Gene | CS |
| UniProt ID | O75390 |
| PDB Structure IDs | 2CTS, 5D0D, 5EAK |
| Molecular Weight | 52 kDa |
| Subcellular Localization | Mitochondria (matrix) |
| Protein Family | Citrate synthase family |
CS is a homodimeric enzyme, with each monomer consisting of two domains: a large domain that forms the core of the enzyme and a small domain that undergoes conformational changes during catalysis. The active site is located at the interface between the two subunits.
Citrate synthase (CS) catalyzes the first and rate-limiting step of the citric acid cycle:
acetyl-CoA + oxaloacetate + H2O → citrate + CoA + H+
This reaction is physiologically irreversible and represents a key regulatory point in metabolism. CS is allosterically regulated by substrate availability and product inhibition.
In neurons, CS is essential for maintaining energy homeostasis and provides citrate for lipid biosynthesis. It is one of the most abundant mitochondrial proteins.
CS activity is often used as a marker for mitochondrial content in cells. It is sensitive to oxidative stress and its activity decreases with aging and in neurodegenerative diseases.
Alzheimer Disease: CS activity is significantly reduced in AD brains, contributing to impaired energy metabolism and neuronal dysfunction. This is one of the earliest metabolic defects observed in AD.
Parkinson Disease: CS activity is reduced in PD brains and in cellular models of PD. Preserving CS function may protect dopaminergic neurons.
Cardiomyopathy: CS deficiency leads to mitochondrial myopathy and cardiomyopathy due to impaired energy production.
Aging: CS activity declines with age, contributing to age-related metabolic decline.
There are currently no drugs directly targeting CS in clinical use for neurodegeneration. Research focuses on: