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. D-threo-isocitrate = glyoxylate + succinate Inhibited by itaconate, itaconic anhydride, bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows on fatty acids, but not on glucose. Succinate at 5 mM inhibits the activity to approximately 50%. kcat is 1.38 sec(-1) for isocitrate lyase activity with threo-DL-isocitrate as substrate (at pH 6). Carbohydrate metabolism; glyoxylate cycle; (S)-malate from isocitrate: step 1/2. Induced by palmitate, acetate and glucose. Repressed by succinate. Deletion of icl2 has a little effect on replication in media containing glycerol, glucose, short-chain fatty acids or long-chain fatty acids. Cells lacking icl2 have no discernible impact on the kinetics of M.tuberculosis growth and persistence. However 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.