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Zinc Inhibition of Mitochondrial Aconitase and Its Importance in Citrate Metabolism of Prostate Epithelial Cells
Open accessAbstract
Prostate epithelial cells possess a uniquely limiting mitochondrial (m-) aconitase activity that minimizes their ability to oxidize citrate. These cells also possess uniquely high cellular and mitochondrial zinc levels. Correlations among zinc, citrate, and m-aconitase in prostate indicated that zinc might be an inhibitor of prostate m-aconitase activity and citrate oxidation. The present studies reveal that zinc at near physiological levels inhibited m-aconitase activity of mitochondrial sonicate preparations obtained from rat ventral prostate epithelial cells. Corresponding studies conducted with mitochondrial sonicates of rat kidney cells revealed that zinc also inhibited the kidney m-aconitase activity. However the inhibitory effect of zinc was more sensitive with the prostate m-aconitase activity. Zinc inhibition fit the competitive inhibitor model. The inhibitory effect of zinc occurred only with citrate as substrate and was specific for the citrate --> cis-aconitate reaction. Other cations (Ca2+, Mn2+, Cd2+) did not result in the inhibitory effects obtained with zinc. The presence of endogenous zinc inhibited the m-aconitase activity of the prostate mitochondrial preparations. Kidney preparations that contain lower endogenous zinc levels exhibited no endogenous inhibition of m-aconitase activity. Studies with pig prostate and seminal vesicle mitochondrial preparations also revealed that zinc was a competitive inhibitor against citrate of m-aconitase activity. The effects of zinc on purified beef heart m-aconitase verified the competitive inhibitor action of zinc. In contrast, zinc had no inhibitory effect on purified cytosolic aconitase. These studies reveal for the first time that zinc is a specific inhibitor of m-aconitase of mammalian cells. In prostate epithelial cells, in situ mitochondrial zinc levels inhibit m-aconitase activity, which provides a mechanism by which citrate oxidation is limited.
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Cited by
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Metadata
- Authors
- Costello, L. C., Liu, Y., Franklin, R. B., & Kennedy, M. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 272
- Issue
- 46
- Pages
- 28875-28881
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2092473371
- Cited by
- 267
- References
- 0
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Zinc Inhibition of Mitochondrial Aconitase and Its Importance in Citrate Metabolism of Prostate Epithelial Cells. https://app.cochat.ai/papers/10.1074/jbc.272.46.28875
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- Costello, L. C., Liu, Y., Franklin, R. B., & Kennedy, M. C. (1997). Zinc Inhibition of Mitochondrial Aconitase and Its Importance in Citrate Metabolism of Prostate Epithelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.46.28875
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