Zinc causes a shift toward citrate at equilibrium of the m-aconitase reaction of prostate mitochondria

Prostate secretory epithelial cells have the unique function and capability of accumulating and secreting extraordinarily high levels of citrate. To a chieve this, these cells possess a uniquely limiting mitochondrial (m)-acon itase activity that minimizes the oxidation of citrate via the Krebs cycle. The steady-state citrate/isocitrate ratio of mammalian tissues is generall y maintained at about 10-11/1, 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 30-40/1. Zinc, which is also accumulated in prostate cells at much higher levels than in other cells, inhibits m-aconitase activity thereby m inimizing citrate oxidation. This current report is concerned with an effec t of zinc on the equilibrium of the reaction catalyzed by m-aconitase. Stud ies were conducted with mitochondrial extract preparations from rat ventral prostate epithelial cells. With citrate as the initial substrate, the addi tion of zinc (7-10 mu M) to the prostate mitochondrial preparation resulted in a change in the citrate/isocitrate ratio at equilibrium from an average of 10.5/1 to 13.5/1. In contrast, the identical treatment of kidney mitoch ondrial preparations resulted in no zinc-induced change in the citrate/isoc itrate ratio. When either cis-aconitate or isocitrate was employed as the i nitial substrate, the addition of zinc did not alter the citrate/isocitrate ratio of prostate or kidney preparations. Partial purification of the pros tate 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 ra tio. This novel effect of zinc provides another mechanism by which it is as sured that the accumulation of citrate is maximized in citrate-producing pr ostate epithelial cells. (C) 2000 Elsevier Science Inc. All rights reserved .