ZINC INHIBITION OF MITOCHONDRIAL ACONITASE AND ITS IMPORTANCE IN CITRATE METABOLISM OF PROSTATE EPITHELIAL-CELLS

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 zin c levels, Correlations among zinc, citrate, and m-aconitase in prostat e indicated that zinc might be an inhibitor of prostate m-aconitase ac tivity and citrate oxidation, The present studies reveal that zinc at near physiological levels inhibited m-aconitase activity of mitochondr ial sonicate preparations obtained from rat ventral prostate epithelia l cells, Corresponding studies conducted with mitochondrial sonicates of rat kidney cells revealed that zinc also inhibited the kidney m-aco nitase activity, However the inhibitory effect of zinc was more sensit ive with the prostate m-aconitase activity. Zinc inhibition fit the co mpetitive inhibitor model, The inhibitory effect of zinc occurred only with citrate as substrate and was specific for the citrate --> cis-ac onitate reaction. Other cations (Ca2+, Mn2+, Cd2+) did not result in t he inhibitory effects obtained with zinc, The presence of endogenous z inc inhibited the m-aconitase activity of the prostate mitochondrial p reparations, Kidney preparations that contain lower endogenous zinc le vels exhibited no endogenous inhibition of m-aconitase activity, Studi es with pig prostate and seminal vesicle mitochondrial preparations al so revealed that zinc was a competitive inhibitor against citrate of m -aconitase activity, The effects of zinc on purified beef heart m-acon itase verified the competitive inhibitor action of zinc, In contrast, zinc had no inhibitory effect on purified cytosolic aconitase, These s tudies 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.