Isocitrate Lyase (ICL) is a metabolic enzyme that converts the metabolite isocitrate into glyoxylate and succinate. ICL is a homotetramer with each monomer being composed of 14 alpha helices, 14 beta sheets, and a magnesium ion cofactor. ICL has shown clinical relevance in the disease state Tuberculosis where it is responsible for the persistence of Mycobacterium tuberculosis during the chronic stage of infection. This survival strategy mediated by ICL is characterized by a metabolic shortcut within the Citric Acid Cycle. ICL creates this shunt pathway by converting isocitrate to succinate and glyoxylate, diverting acetyl-CoA from the beta-oxidation of fatty acids.
Figure 1: ICL mediated glyoxylate shunt pathway of the Citric Acid Cycle
Structure
Active Site
Mechanism
Chemical Mechanism of Isocitrate Lyase
