The cause of
Fanconi syndrome in
cystinosis is enigmatic. It has previously been shown that renal tubules could be loaded with
cystine by incubating them with
cystine dimethylester (CDE), mimicking the biochemical hallmark of
cystinosis. Such tubules have impaired transport, decreased whole-cell O2 consumption, and substrate utilization. In this study, the metabolic disturbances in
cystine-loaded renal tubule cells were further characterized. Isolated rat renal tubules were loaded with
cystine by incubating them with 2 mM CDE for 10 min. This had no significant effect on total
ATPase, Na(+)-K(+)-
ATPase, or the
ouabain-insensitive
ATPase activity of renal tissue homogenates from these
cystine-loaded tubules. Intracellular K was significantly lower in the
cystine-loaded tubules (37 +/- 2 versus 47 +/- 3 nEq/mg; P < 0.008). Intracellular
ATP was reduced by 39% in the
cystine-loaded tubules (23.7 +/- 2.4 versus 38.1 +/- 3.3 nmol/mg of
protein; P < 0.0025). CDE (2 mM) reduced isolated mitochondrial O2 consumption with
glutamate as the substrate by 66% (4.7 +/- 0.7 versus 13.9 +/- 0.8 nm/min per mg of
protein, P < 0.001) but had no effect on mitochondrial O2 consumption with
succinate as the substrate. It was speculated that the impaired transport from
cystine loading with CDE is secondary to a decrease in energy generation.