CitratSynthase

CitratSynthase, more commonly known as citrate synthase, is a key enzyme of cellular metabolism that catalyzes the first step of the citric acid cycle. It facilitates the condensation of acetyl-CoA and oxaloacetate to form citrate, releasing CoA-SH in the process. This reaction connects the metabolism of carbohydrates, fats, and proteins to energy production in aerobic respiration and takes place in the mitochondrial matrix of eukaryotes and in the cytosol of many prokaryotes.

Structure and variants: Most citrate synthases function as homo-dimers. Some bacterial enzymes belong to a type II family that assembles as hexamers and can display different regulatory features. Eukaryotic mitochondrial CS is typically a dimer and is synthesized with a short N-terminal targeting sequence for import into mitochondria.

Mechanism and regulation: The reaction proceeds via formation of a citryl-CoA intermediate, followed by hydrolysis to citrate and CoA. The enzyme provides a binding site that aligns substrates for condensation. Citrate synthase activity is regulated by cellular energy status and can be subject to feedback inhibition by high NADH and other metabolites in some organisms; Ca2+ can modulate activity of CS as part of coordinated control of the TCA cycle in muscle and other tissues.

Clinical and research relevance: Defects in citrate synthase are rare but can cause metabolic disorders in humans. The enzyme is a central model for understanding enzyme catalysis and metabolic regulation and is widely used in studies of metabolism, bioenergetics, and metabolic engineering for citrate production.