Alteration of Oxidative Phos phorylation in Uremia

The effect of ultrafiltrate of uremic serum upon the oxygen consumption of rat liver mitochondria was studied. Oxygen consumption in the absence of adenosine diphosphate (State 4) was increased by the addition of ultrafiltered serum of uremic patients, causing decrease of P/O ratio and respiratory control ratio, indicating the uncoupler action of uremic serum. Such uncoupler action was noted when succinate was used as the substrate, and also when α-ketoglutarate was used as the nicotinamide adenine dinucleotide-linked substrate. The mitochondrial respiration in the presence of adenosine diphosphate (State 3) was decreased, suggesting the inhibitory action of uremic serum on energy transfer. Oxygen consumption after 20 minute incubation with uremic serum showed the decrease in either state, leaving ground for the presence of inhibitory action against electron transport. Similar results were obtained in liver mitochondria of rats in acute renal insufficiency caused by bilateral nephrectomy. Based on these facts, the nature of metabolic inhibitors in uremic serum was discussed.