title: Zinc causes a shift toward citrate at equilibrium of the m-aconitase reaction of prostate mitochondria.
abstract: Prostate secretory epithelial cells have the unique function and capability of accumulating and secreting extraordinarily high levels of citrate. To achieve this, these cells possess a uniquely limiting mitochondrial (m)-aconitase activity that minimizes the oxidation of citrate via the Krebs cycle. The steady-state citrate/isocitrate ratio of mammalian tissues is generally maintained at about 10-11/l, independent of the concentration of citrate, which is the result of the chemical equilibrium reached in the presence of m-aconitase. In contrast, the citrate/isocitrate ratio of prostate tissue is about 30-40/l. Zinc, which is also accumulated in prostate cells at much higher levels than in other cells, inhibits m-aconitase activity thereby minimizing citrate oxidation. This current report is concerned with an effect of zinc on the equilibrium of the reaction catalyzed by m-aconitase. Studies were conducted with mitochondrial extract preparations from rat ventral prostate epithelial cells. With citrate as the initial substrate, the addition of zinc (7-10 microM) to the prostate mitochondrial preparation resulted in a change in the citrate/isocitrate ratio at equilibrium from an average of 10.5/l to 13.5/l. In contrast, the identical treatment of kidney mitochondrial preparations resulted in no zinc-induced change in the citrate/isocitrate ratio. When either cis-aconitate or isocitrate was employed as the initial substrate, the addition of zinc did not alter the citrate/isocitrate ratio of prostate or kidney preparations. Partial purification of the prostate preparation revealed that the prostate mitochondrial extract contained a putative protein (which we have designated as 'citrate factor protein') that is required for the zinc-induced increase in the citrate/isocitrate ratio. This novel effect of zinc provides another mechanism by which it is assured that the accumulation of citrate is maximized in citrate-producing prostate epithelial cells.
authors.affiliation: Cellular and Molecular Biology Section, OCBS/Dental School, University of Maryland, Baltimore 21201, USA. lcc001@dental.umaryland.edu
authors.forename: L C
authors.initials: LC
authors.lastname: Costello
authors.forename: R B
authors.initials: RB
authors.lastname: Franklin
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M C
authors.initials: MC
authors.lastname: Kennedy
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D011467:Prostate / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000378:metabolism*
chemical_list: D000154:Aconitate Hydratase; D015032:Zinc