Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates. It also catalyzes the formation of pyruvate and succinate from 2-methylisocitrate, a key step in the methylcitrate cycle (propionate degradation route). D-threo-isocitrate = glyoxylate + succinate (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + succinate Can also use Mn(2+) ion. Inhibited by itaconate, itaconic anhydride, bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows on fatty acids, but not on glucose. At 5 mM, oxalate and malate also inhibit the activity to approximately 50%. kcat is 5.24 sec(-1) for isocitrate lyase activity with threo-DL-isocitrate as substrate (at pH 6). kcat is 1.25 sec(-1) for methylisocitrate lyase activity with DL-threo-2-methylisocitrate as substrate (at pH 7.5). Optimum pH is 6.8. Carbohydrate metabolism; glyoxylate cycle; (S)-malate from isocitrate: step 1/2. Homotetramer. Induced by palmitate and acetate. Repressed by glucose and succinate. Deletion of icl1 has little effect on replication in media containing glycerol, glucose, short-chain fatty acids or long-chain fatty acids. Deletion of icl1 results in a modest reduction of the bacterial load in the lungs during the chronic phase but not the acute phase of infection, and reduces tissue pathology. Deletion of both icl1 and icl2 eliminates growth on fatty acids but has little effect on use of carbohydrates. Cells lacking both genes are incapable of growth in mice and are rapidly eliminated from the lungs and spleen. Belongs to the isocitrate lyase/PEP mutase superfamily. Isocitrate lyase family.