Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia.
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 mitochondrial aconitase (m-aconitase), the first step in mitochondrial citrate metabolism, in these conditions.


METHODS
Rats were fed appropriate diets, and m-aconitase activity and protein abundance measured.


RESULTS
In chronic metabolic acidosis and 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 with 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 mitochondrial 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.
Melnick
J Z
JZ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA. j-melnick@nwu.edu
Preisig
P A
PA
Moe
O W
OW
Srere
P
P
Alpern
R J
RJ
D000138:Acidosis / Q000178:diet therapy / Q000378:metabolism*; D000154:Aconitate Hydratase / Q000032:analysis / Q000378:metabolism*; D000468:Alkalies / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002951:Citrates / Q000652:urine*; D004032:Diet; D007669:Kidney Calculi / Q000178:diet therapy / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D011191:Potassium Deficiency / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000468:Alkalies; D002951:Citrates; D002950:Citrate (si)-Synthase; D000154:Aconitate Hydratase