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- W188410144 abstract "The prostate contains much higher levels of both citrate and zinc (mM) than is found in other tissues of the body. It has been proposed that the elevated levels of citrate arise from inhibition of prostate aconitase by zinc. In light of this work and in attempting to generate a mixed metal cluster in aconitase and similar Fe-S containing enzymes, the authors have examined the effect of Zn{sup 2+} and other divalent metals on several Fe-S containing enzymes. Spectroscopic data show that inactivation is concomitant with destruction of the Fe-S cluster. The rates of inactivation by the divalent form of first row transition metals follow the Irving-Williams series for metal-ligand stabilities: Mn{sup 2+} {lt} Co{sup 2+} {lt} Ni{sup 2+} {lt} Cu{sup 2+} {gt} Zn{sup 2+}. Unlike inhibition by substrate analogs or inactivation by oxidants of the Fe-S cluster, citrate does not substantially protect aconitase. The rate of inactivation of aconitase by Zn{sup 2+} at pH 7 is 3 M{sup {minus}1}s{sup {minus}1} for substrate-free enzyme and 1 M{sup {minus}1}s{sup {minus}1} for the enzyme-substrate complex. From these results the authors postulate that aconitase inhibition by Zn{sup 2+} derives from the formation of ZnS with concomitant cluster destruction and enzyme inactivation. Since amore » common theme found in several hydro-lyases like aconitase is catalysis by an Fe-S cluster, the authors have also examined other Fe-S enzymes for their susceptibility to inactivation by divalent metals. The authors find that fumarase A and dihydroxyacid dehydratase, both isolated from E. coli, and yeast isopropylmalate isomerase are also inactivated by divalent metals. In contrast, various ferredoxins appear to be quite stable in the presence of mM quantities of divalent metals.« less" @default.
- W188410144 created "2016-06-24" @default.
- W188410144 creator A5063032565 @default.
- W188410144 date "1991-03-11" @default.
- W188410144 modified "2023-09-26" @default.
- W188410144 title "Inactivation of aconitase and similar Fe-S containing enzymes by divalent metals" @default.
- W188410144 hasPublicationYear "1991" @default.
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