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The inactivation of Fe-S cluster containing hydro-lyases by superoxide.
J Biol Chem. 1993 Oct 25; 268(30):22369-76.JB

Abstract

We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in the range of 10(6) to 10(7) M-1 s-1. Each of these enzymes belongs to the hydro-lyase class and contains catalytically active [4Fe-4S] clusters. Simultaneous with inactivation by O2- is the release of iron from their clusters. Our working hypothesis is O2- inactivates these enzymes by oxidizing their clusters to an unstable oxidation state, and cluster degradation follows. Consistent with this hypothesis is our observation that spinach dihydroxy-acid dehydratase, a member of the hydro-lyase class that has a catalytically active [2Fe-2S] cluster, is not inactivated and does not lose iron in the presence of O2-. Porcine fumarase, a member of the hydro-lyase class that does not contain an Fe-S cluster, is also not inactivated by O2-. We also report the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase by O2 are close to 2 x 10(2) M-1 s-1, and the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase and mammalian aconitase by H2O2 are about 10(3) M-1 s-1. E. coli dihydroxy-acid dehydratase has been reported previously to be inactivated in vivo when cells are grown in hyperbaric O2, presumably due to the increased O2- generated under these conditions. We report here that E. coli fumarase A, fumarase B, and aconitase are also inactivated in vivo by hyperbaric O2. Thermodynamic parameters for the oxidation of the cluster of aconitase by O2- and O2 are calculated.

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Authors+Show Affiliations

Flint DH
E. I. du Pont de Nemours and Company, Central Research and Development, Experimental Station, Wilmington, Delaware 19880.
Tuminello JF
No affiliation info available
Emptage MH
No affiliation info available

MeSH

Aconitate HydrataseAnimalsEscherichia coliFumarate HydrataseHydro-LyasesIronIron-Sulfur ProteinsIsoenzymesKineticsMammalsMathematicsMitochondriaModels, TheoreticalSuperoxidesVegetables

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8226748

Citation

Flint, D H., et al. "The Inactivation of Fe-S Cluster Containing Hydro-lyases By Superoxide." The Journal of Biological Chemistry, vol. 268, no. 30, 1993, pp. 22369-76.
Flint DH, Tuminello JF, Emptage MH. The inactivation of Fe-S cluster containing hydro-lyases by superoxide. J Biol Chem. 1993;268(30):22369-76.
Flint, D. H., Tuminello, J. F., & Emptage, M. H. (1993). The inactivation of Fe-S cluster containing hydro-lyases by superoxide. The Journal of Biological Chemistry, 268(30), 22369-76.
Flint DH, Tuminello JF, Emptage MH. The Inactivation of Fe-S Cluster Containing Hydro-lyases By Superoxide. J Biol Chem. 1993 Oct 25;268(30):22369-76. PubMed PMID: 8226748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The inactivation of Fe-S cluster containing hydro-lyases by superoxide. AU - Flint,D H, AU - Tuminello,J F, AU - Emptage,M H, PY - 1993/10/25/pubmed PY - 1993/10/25/medline PY - 1993/10/25/entrez SP - 22369 EP - 76 JF - The Journal of biological chemistry JO - J Biol Chem VL - 268 IS - 30 N2 - We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in the range of 10(6) to 10(7) M-1 s-1. Each of these enzymes belongs to the hydro-lyase class and contains catalytically active [4Fe-4S] clusters. Simultaneous with inactivation by O2- is the release of iron from their clusters. Our working hypothesis is O2- inactivates these enzymes by oxidizing their clusters to an unstable oxidation state, and cluster degradation follows. Consistent with this hypothesis is our observation that spinach dihydroxy-acid dehydratase, a member of the hydro-lyase class that has a catalytically active [2Fe-2S] cluster, is not inactivated and does not lose iron in the presence of O2-. Porcine fumarase, a member of the hydro-lyase class that does not contain an Fe-S cluster, is also not inactivated by O2-. We also report the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase by O2 are close to 2 x 10(2) M-1 s-1, and the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase and mammalian aconitase by H2O2 are about 10(3) M-1 s-1. E. coli dihydroxy-acid dehydratase has been reported previously to be inactivated in vivo when cells are grown in hyperbaric O2, presumably due to the increased O2- generated under these conditions. We report here that E. coli fumarase A, fumarase B, and aconitase are also inactivated in vivo by hyperbaric O2. Thermodynamic parameters for the oxidation of the cluster of aconitase by O2- and O2 are calculated. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8226748/The_inactivation_of_Fe_S_cluster_containing_hydro_lyases_by_superoxide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)41538-4 DB - PRIME DP - Unbound Medicine ER -