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Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells.
J Biol Chem. 1997 Nov 14; 272(46):28875-81.JB

Abstract

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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Authors+Show Affiliations

Costello LC
Cellular and Molecular Biology Section/Oral Craniofacial and Biological Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201, USA. lcostell@umabnet.ab.umd.edu
Liu Y
No affiliation info available
Franklin RB
No affiliation info available
Kennedy MC
No affiliation info available

MeSH

Aconitate HydrataseAnimalsCitratesEpithelial CellsKidneyMaleMitochondriaProstateRatsRats, WistarSubstrate SpecificityZinc

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9360955

Citation

Costello, L C., et al. "Zinc Inhibition of Mitochondrial Aconitase and Its Importance in Citrate Metabolism of Prostate Epithelial Cells." The Journal of Biological Chemistry, vol. 272, no. 46, 1997, pp. 28875-81.
Costello LC, Liu Y, Franklin RB, et al. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem. 1997;272(46):28875-81.
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. The Journal of Biological Chemistry, 272(46), 28875-81.
Costello LC, et al. Zinc Inhibition of Mitochondrial Aconitase and Its Importance in Citrate Metabolism of Prostate Epithelial Cells. J Biol Chem. 1997 Nov 14;272(46):28875-81. PubMed PMID: 9360955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. AU - Costello,L C, AU - Liu,Y, AU - Franklin,R B, AU - Kennedy,M C, PY - 1997/11/20/pubmed PY - 1997/11/20/medline PY - 1997/11/20/entrez SP - 28875 EP - 81 JF - The Journal of biological chemistry JO - J Biol Chem VL - 272 IS - 46 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9360955/Zinc_inhibition_of_mitochondrial_aconitase_and_its_importance_in_citrate_metabolism_of_prostate_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)50831-0 DB - PRIME DP - Unbound Medicine ER -