Citrate synthase, mitochondrial (CS)

Citrate synthase is the pace-making enzyme of the mitochondrial tricarboxylic acid (TCA) cycle, catalyzing the condensation of acetyl-CoA and oxaloacetate to form citrate (UniProt O75390). This reaction represents the first and rate-limiting step of the cycle, making it essential for aerobic energy production and the generation of metabolic intermediates (Wikipedia). In oncology, citrate synthase is often upregulated to support the high biosynthetic demands of proliferating cells, and its knockdown has been shown to suppress tumor growth in various cancer models (NIH 2.4.2). Conversely, its activity is significantly reduced in neurodegenerative diseases like Alzheimer's, where it contributes to bioenergetic failure and impaired acetylcholine synthesis (PubMed 37393492). Recent research also highlights its role in sepsis, where serum levels of the enzyme may serve as a biomarker for mitochondrial dysfunction and organ injury (bioRxiv 2.3.5). While it is a critical metabolic hub, the development of therapeutic inhibitors is challenged by the enzyme's essential role in all aerobic tissues, necessitating strategies for tissue-specific or tumor-selective modulation (SCBT).

Other names

Citrate (Si)-synthaseCISY_HUMANCIT

Catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate and coenzyme A (CoA) in the first step of the TCA cycle (Wikipedia). Inhibitors typically act as substrate analogues or through feedback inhibition by products like ATP and NADH (SCBT).