Unconventional Iron-Sulfur Clusters in Mitochondrial Enzymes

  • Thomas P. Singer


It is a common misconception that the more we learn about a scientific phenomenon, the simpler its explanation becomes. At least in the field of membrane-bound Fe-S enzymes, the opposite seems to have happened. When metal flavoproteins were first discovered, it was often concluded that nonheme Fe was an integral component of an enzyme, solely on the basis of finding it in purified preparations, and if the enzyme was inhibited by Fe clusters, this seemed to justify the conclusion that the metal functioned in catalysis. When it was recognized that such evidence is usually insufficient and frequently misleading (Singer and Massey, 1957), new and less ambiguous approaches were sought. The discovery that succinate and NADH dehydrogenases in membrane preparations exhibited an EPR signal at g ~ 1.94 on reduction by substrate and the recognition that an iron compound was probably responsible for this signal (Beinert and Sands, 1960) provided a powerful new tool for the study of nonheme iron function in enzymes. When combined with the freeze-quench method (Bray, 1961) for the study of rapid reactions, this permitted following the changes in the redox state of the Fe during catalysis. In a few cases it could even be shown that the rate of appearance of this reduced iron signal agreed well with the turnover rate measured in steady-state assays (Rajagopalan and Handler, 1968).


Succinate Dehydrogenase NADH Dehydrogenase Soluble Sample Trinuclear Cluster Soluble Preparation 
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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Thomas P. Singer
    • 1
    • 2
  1. 1.Molecular Biology DivisionVeterans Administration Medical CenterSan FranciscoUSA
  2. 2.Department of Biochemistry and BiophysicsUniversity of CaliforniaSan FranciscoUSA

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