RENAL CORTICAL MITOCHONDRIAL ACONITASE IS REGULATED IN HYPOCITRATURIAAND HYPERCITRATURIA

Background.Chronic metabolic acidosis and K+ deficiency increase, whil e alkali feeding decreases proximal tubule citrate absorption and meta bolism. The present studies examined the regulation of mitochondrial a conitase (m-aconitase), the first step in mitochondrial citrate metabo lism, in these conditions. Methods. Rats were fed appropriate diets, a nd m-aconitase activity and protein abundance measured. Results. In ch ronic metabolic acidosis and chronic K+ deficiency. renal cortical m-a conitase activity was increased 17% and 43%, respectively. This was as sociated with respective 90% and 221% increases in renal cortical m-ac onitase protein abundance. With chronic alkali feeding, there was a 12 % decrease in renal cortical m-aconitase activity, associated with a 3 5% decrease in m-aconitase protein abundance. Hepatic m-aconitase acti vity was not regulated in a similar manner. There was no regulation of citrate: synthase, the enzyme responsible for mitochondrial citrate s ynthesis. Conclusion. These studies demonstrate tissue specific chroni c regulation of renal cortical m-aconitase activity and protein abunda nce, which likely contributes to the hypocitraturia and hypercitraturi a seen in these conditions. As m-aconitase is the only step in citrate transport and metabolism found to be regulated in alkali feeding, its regulation likely plays a significant role in mediating the hypercitr aturia seen in this condition.