TY - JOUR
T1 - Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia
AU - Melnick, Joel Z.
AU - Preisig, Patricia A.
AU - Moe, Orson W.
AU - Srere, Paul
AU - Alpern, Robert J.
N1 - Funding Information:
The authors gratefully acknowledge the technical assistance of Martha Ferguson and Hsin-Yi Chang. These studies were supported by a grant from the NIH P01-DK20543 (RJA) and the Veterans Administration (OWM and PS). JZM was supported by NIH institutional training grant T32-DK07659 and a grant from Northwestern University.
PY - 1998
Y1 - 1998
N2 - Background. Chronic metabolic acidosis and K(±) deficiency increase, while alkali feeding decreases proximal tubule citrate absorption and metabolism. The present studies examined the regulation of mithochondrial aconitase (m-aconitase), the first step in mithochondrial citrate metabolism, in these conditions. Methods. Rats were fed appropriate diets, and m- aconitase activity and protein abundance measured. Results. In chronic metabolic acidosis anf chronic K(±) deficiency, renal cortical m-aconitase activity was increased 17% and 43%, respectively. This was associated with respective 90% and 221% increases in renal cortical m-aconitase protein abundance. With chronic alkali feeding, there was a 12% decrease in renal cortical m-aconitase activity, associated witlh a 35% decrease in m-aconitase protein abundance. Hepatic m-aconitase activity was not regulated in a similar manner. There was no regulation of citrate synthase, the enzyme responsible for mithochondrial citrate synthesis. Conclusions. These studies demonstrate tissue specific chronic regulation of renal cortical m-aconitase activity and protein abundance, which likely contributes to the hypocitraturia and hypercitraturia 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 hypercitraturia seen in this condition.
AB - Background. Chronic metabolic acidosis and K(±) deficiency increase, while alkali feeding decreases proximal tubule citrate absorption and metabolism. The present studies examined the regulation of mithochondrial aconitase (m-aconitase), the first step in mithochondrial citrate metabolism, in these conditions. Methods. Rats were fed appropriate diets, and m- aconitase activity and protein abundance measured. Results. In chronic metabolic acidosis anf chronic K(±) deficiency, renal cortical m-aconitase activity was increased 17% and 43%, respectively. This was associated with respective 90% and 221% increases in renal cortical m-aconitase protein abundance. With chronic alkali feeding, there was a 12% decrease in renal cortical m-aconitase activity, associated witlh a 35% decrease in m-aconitase protein abundance. Hepatic m-aconitase activity was not regulated in a similar manner. There was no regulation of citrate synthase, the enzyme responsible for mithochondrial citrate synthesis. Conclusions. These studies demonstrate tissue specific chronic regulation of renal cortical m-aconitase activity and protein abundance, which likely contributes to the hypocitraturia and hypercitraturia 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 hypercitraturia seen in this condition.
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U2 - 10.1046/j.1523-1755.1998.00974.x
DO - 10.1046/j.1523-1755.1998.00974.x
M3 - Article
C2 - 9648074
AN - SCOPUS:0031806539
SN - 0085-2538
VL - 54
SP - 160
EP - 165
JO - Kidney international
JF - Kidney international
IS - 1
ER -