Aconitate hydratase (Aconitase)

Aconitate hydratase (commonly known as aconitase) is an iron-sulfur enzyme that catalyzes the stereospecific isomerization of citrate to isocitrate via the intermediate cis-aconitate, a critical step in the citric acid (TCA) cycle[1][3][4][6]. Aconitase contains a [4Fe-4S] iron-sulfur cluster essential for its catalytic activity and is widely expressed from bacteria to humans, with both mitochondria-specific (ACO2) and cytosolic (ACO1) isoforms in eukaryotes. By enabling the TCA cycle, aconitase plays a central role in aerobic energy metabolism. The enzyme is sensitive to oxidative stress due to its iron-sulfur prosthetic group, and its activity is a marker for mitochondrial health. Dysfunction or inhibition of aconitase contributes to metabolic diseases, neurodegenerative conditions, and cancer cell metabolism adaptations[1][4][6].

Other names

AconitaseCitrate hydro-lyaseACO1 (gene, isoform in plants)ACO2 (mitochondrial isoform in humans)

Inhibitors block the isomerization of citrate to isocitrate by binding the active site or disrupting the iron-sulfur cluster[1][4]. Drugs that target the enzyme block cellular energy metabolism and the TCA cycle.