AJP - Renal Physiology, Vol 250, Issue 4 667-F673, Copyright © 1986 by American Physiological Society
Renal mitochondrial glutamine metabolism during K+ depletion
S. Sastrasinh and M. Sastrasinh
We studied changes in renal mitochondrial glutamine metabolism during the
development of and recovery from K+ depletion in rats. Significant increase
in mitochondrial NH3 production was noted after 3 days of K+-free diet.
Ammoniagenesis in K+-depleted animals reached maximal level within 2 wk of
K+ deprivation when there was 64% increase in NH3 production. In contrast
to the pattern of changes in mitochondrial ammoniagenesis,
phosphate-dependent glutaminase (PDG) activity increased within the first
48 h of K+ deprivation, before there was any increase in NH3 production,
and did not plateau even after 2 wk of K+-free diet. The disparity between
NH3 production and PDG activity cannot be explained by the difference in
matrix glutamate level, thus raising the possibility that mitochondrial
glutamine entry may be a rate-limiting step for ammoniagenesis during K+
depletion. Recovery from K+ depletion was studied in animals prefed with
K+-free diet for 2 wk prior to the initiation of K+-supplemented diet.
Muscle K+ content of K+-depleted animals returned to normal after 1 wk of
K+ replacement. Mitochondrial NH3 production decreased concomitantly with
the attenuation in K+ deficit but did not reach the base-line value even
after K+ deficit was completely corrected. Additional experiments with
isolated cortical tubules also showed persistent increase in NH3 production
after the correction of K+ deficit. Thus, unlike earlier studies in rats
during the recovery from metabolic acidosis, which showed only increased
ammoniagenesis in isolated mitochondria but not in cortical slices, animals
recovered from K+ depletion demonstrated augmented NH3 production both in
isolated mitochondria and intact renal tissues.
