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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: itaconate degradation

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: 2-methylsuccinate degradation

Superclasses: Degradation/Utilization/Assimilation Carboxylates Degradation

Some taxa known to possess this pathway include ? : Pseudomonas fluorescens , Pseudomonas sp. B2aba

Expected Taxonomic Range: Bacteria , Opisthokonta

Summary:
itaconate is an unsaturated acid with conjugated double bonds and two carboxyl groups. The acid was discovered in 1837 [Baup37], and was named itaconate as an anagram of cis-aconitate, from which it was first derived by Crasso in 1840 [Turner41].

Because of its unique structure and characteristics, itaconate and its ester are useful materials for the bioindustry. It is used for the synthesis of fiber, resin, plastic, rubber, paints, surfactant, ion-exchange resins and lubricant [Dwiarti07].

Many microorganisms are able to grow on itaconate as their sole source of carbon [Nagai63, Brightman61]. In addition, itaconate is oxidized in liver mitochondria in a pathway that involves activation to itaconyl-CoA followed by hydration and cleavage to yield acetyl-CoA and pyruvate [Adler57, Wang61].

Pseudomonas sp. B2aba was shown to employ a pathway that is very similar to that found in liver mitochondria [Cooper64]. When cell-free extracts were incubated with itaconate, Mg2+, ions, coenzyme A and ATP, pyruvate was formed. The amount of pyruvate formed was proportional to the quantities of coenzyme A added. Synthetic itaconyl-CoA could replace itaconate , coenzyme A and ATP, suggesting that itaconate is first activated to itaconyl-CoA.

In addition, washed suspensions of Pseudomonas sp. B2aba grown on itaconate readily oxidized (S)-citramalate, whereas washed suspensions of the organism grown on succinate did not. Further studies established that in the presence of succinyl-CoA and itaconate (3S)-citramalyl-CoA is formed as an intermediate in the pathway. A similar conculsion was arrived in an earlier study with Pseudomonas fluorescens [Nagai63].

The three enzymes succinyl-CoA:itaconate CoA transferase, itaconyl-CoA hydratase and citramalyl-CoA lyase were partially purifed, and shown to catalyze the conversion of itaconate to pyruvate and acetyl-CoA in vitro. The first enzyme was also able to accept (S)-citramalate as substrate, enabling the organism to grow on (S)-citramalate. All of these enzymes were induced by growth on itaconate, (S)-citramalate or methylsuccinate.

A fourth enzyme, itaconyl-CoA synthetase, was isolated and shown to form itaconyl-CoA from itaconate. This enzyme was shown to be identical to (GDP-forming) succinyl-CoA synthetase, and was not inducible [Cooper64].

An identical pathway was also reported in a Micrococcus sp. [Cooper65a].

Credits:
Created 13-Dec-2007 by Caspi R , SRI International


References

Adler57: Adler, J., Wang, S.F., Lardy, H.A. (1957). "The metabolism of itaconic acid by liver mitochondria." J Biol Chem 229(2);865-79. PMID: 13502348

Baup37: Baup, S. (1837). "Ueber eine neue Pyrogen-Citronensäure und über Benennung der Pyrogen-Säuren überhaupt." Ann Chim Phys 19:29-38.

Brightman61: Brightman V, Martin WR (1961). "Pathway for the dissimilation of itaconic and mesaconic acids." J Bacteriol 82(3);376-82. PMID: 16561921

Cooper64: Cooper RA, Kornberg HL (1964). "The utilization of itaconate by Pseudomonas sp." Biochem J 91(1);82-91. PMID: 4284209

Cooper65a: Cooper, R.A., Itiaba, K., Kornberg, H.L. (1965). "The utilization of aconate and itaconate by Micrococcus sp." Biochem J 94;25-31. PMID: 14342240

Dwiarti07: Dwiarti L, Otsuka M, Miura S, Yaguchi M, Okabe M (2007). "Itaconic acid production using sago starch hydrolysate by Aspergillus terreus TN484-M1." Bioresour Technol 98(17);3329-37. PMID: 17451943

Nagai63: Nagai, J. (1963). "Studies on itaconate metabolism. II. Citramalate metabolism in Pseudomonas fluorescens grown on itaconate." J Biochem (Tokyo) 54;34-40. PMID: 14056350

Turner41: Turner, E. (1841). "Elements of chemistry including the recent discoveries and doctrines of the science." Printed by Taylor and Walton, University College, London.

Wang61: Wang S.F., Adler, J., Lardy, H.A. (1961). "The pathway of itaconate metabolism by liver mitochondria." J Biol Chem 236;26-30. PMID: 13783048

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Buckel76: Buckel W, Bobi A (1976). "The enzyme complex citramalate lyase from Clostridium tetanomorphum." Eur J Biochem 1976;64(1);255-62. PMID: 1278156

Dimroth77: Dimroth P, Buckel W, Loyal R, Eggerer H (1977). "Isolation and function of the subunits of citramalate lyase and formation of hybrids with the subunits of citrate lyase." Eur J Biochem 1977;80(2);469-77. PMID: 923590

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Michelucci13: Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, Balling R, Hiller K (2013). "Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production." Proc Natl Acad Sci U S A 110(19);7820-5. PMID: 23610393

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

Zarzycki09: Zarzycki J, Brecht V, Muller M, Fuchs G (2009). "Identifying the missing steps of the autotrophic 3-hydroxypropionate CO2 fixation cycle in Chloroflexus aurantiacus." Proc Natl Acad Sci U S A 106(50);21317-22. PMID: 19955419


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC14A.