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Literature summary extracted from

  • Eoh, H.; Rhee, K.Y.
    Methylcitrate cycle defines the bactericidal essentiality of isocitrate lyase for survival of Mycobacterium tuberculosis on fatty acids (2014), Proc. Natl. Acad. Sci. USA, 111, 4976-4981.
    View publication on PubMedView publication on EuropePMC

Inhibitors

EC Number Inhibitors Comment Organism Structure
4.1.3.1 Itaconic acid itaconic acid specifically inhibits growth of wild-type cells on acetate and propionate, but not dextrose, in an ICL-dependent manner, and elicited metabolomic changes similar to those observed with ICL-deficient cells. Enzyme ICL inhibition by itaconic acid results in a specific decrease in intrabacterial pH from pH 7.3 to pH 6.4 in propionate-grown cells, not in acetate-grown cells Mycobacterium tuberculosis
4.1.3.30 Itaconic acid itaconic acid specifically inhibits growth of wild-type cells on acetate and propionate, but not dextrose, in an ICL-dependent manner, and elicited metabolomic changes similar to those observed with ICL-deficient cells. Enzyme ICL inhibition by itaconic acid results in a specific decrease in intrabacterial pH from pH 7.3 to pH 6.4 in propionat-grown cells, not in acetate-grown cells Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.1.3.1 isocitrate Mycobacterium tuberculosis
-
 succinate + glyoxylate
-
 ?
4.1.3.1 additional information Mycobacterium tuberculosis Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases, EC 4.1.3.1 and EC 4.1.3.30, required for growth on even and odd chain fatty acids ?
-
 ?
4.1.3.30 (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate Mycobacterium tuberculosis
-
 succinate + pyruvate
-
 ?
4.1.3.30 additional information Mycobacterium tuberculosis Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases, EC 4.1.3.1 and EC 4.1.3.30, required for growth on even and odd chain fatty acids ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
4.1.3.1 Mycobacterium tuberculosis
-
-
-
4.1.3.30 Mycobacterium tuberculosis
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.1.3.1 isocitrate
-
 Mycobacterium tuberculosis succinate + glyoxylate
-
 ?
4.1.3.1 additional information Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases, EC 4.1.3.1 and EC 4.1.3.30, required for growth on even and odd chain fatty acids Mycobacterium tuberculosis ?
-
 ?
4.1.3.30 (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate
-
 Mycobacterium tuberculosis succinate + pyruvate
-
 ?
4.1.3.30 additional information Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases, EC 4.1.3.1 and EC 4.1.3.30, required for growth on even and odd chain fatty acids Mycobacterium tuberculosis ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
4.1.3.1 ICL
-
 Mycobacterium tuberculosis
4.1.3.30 MCL
-
 Mycobacterium tuberculosis

General Information

EC Number General Information Comment Organism
4.1.3.1 malfunction enzyme-deficient cells undergo a progressive depletion of TCA cycle intermediates and accumulation of propionyl-CoA when metabolizing fatty acid substrates, phenotype, overview. Enzyme-deficient cells are unable to metabolize both even- and odd-chain fatty acids because of the dead-end depletion of TCA cycle intermediates by a constitutively active, but broken, methylcitrate cycle. Addition of cobalamin is sufficient to selectively protect ICL-deficient cells from the bactericidal effects of acetate and propionate, and this attenuation is accompanied by a dose-dependent restoration of TCA cycle activity and propionyl-CoA levels Mycobacterium tuberculosis
4.1.3.1 physiological function Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids Mycobacterium tuberculosis
4.1.3.30 malfunction absence of MCL activity results in the accumulation of methylisocitrate as a metabolic dead end product arising from the stoichiometric consumption of oxaloacetate by propionyl-CoA, phenotype, overview. Isocitrate lyases are essential for survival on both acetate and propionate because of its methylisocitrate lyase activity. Lack of methylisocitrate lyase activity converts the cell methylcitrate cycle into a dead end pathway that sequesters tricarboxylic acid (TCA) cycle intermediates into methylcitrate cycle intermediates, depletes gluconeogenic precursors, and results in defects of membrane potential and intrabacterial pH Mycobacterium tuberculosis
4.1.3.30 physiological function Mycobacterium tuberculosis isocitrate lyases are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids Mycobacterium tuberculosis