P: 40 Potassium Deficiency Compromises Urea Synthesis and Markedly Increases Ammonia in Rats

Abstract

BACKGROUND: Potassium deficiency decreases gene expression, synthesis of proteins, and growth in plants, bacteria, rodents and humans.1–4 The effect of hypokalemia on liver protein synthesis is scarcely described. Early studies have established an association between hypokalemia and development of hepatic encephalopathy in chronic liver disease.5,6 We investigated the effects of potassium deficiency on synthesis of liver proteins including urea cycle enzymes and the regulation of urea synthesis in rats. METHODS: Female Wistar rats were fed a K+-free diet for 13 days. Half of the rats were then repleted with K+ for one week following depletion. K+-depleted and -repleted rats were compared to free-fed and pair-fed controls. We examined the urea cycle enzyme mRNAs and proteins in liver tissue, the in vivo Capacity of Urea-Nitrogen Synthesis (CUNS) and plasma ammonia concentrations. Also, we measured hepatic albumin gene and protein expression, and potassium levels in plasma, liver, kidney and muscle tissues. RESULTS: The diet induced hypokalemia of 1.9 ± 0.4 mmol/L compared to pair-fed controls (3.6 ± 0.2 mmol/L). Muscle and kidney tissue potassium concentrations were decreased, but unchanged in liver tissue. Gene expression of albumin and two out of five urea cycle enzymes were moderately decreased, whereas protein expressions of albumin, the urea cycle enzymes, and glutamine synthetase were normal. However, CUNS was reduced by 33%. Plasma ammonia concentrations were eight-fold elevated to 235 (95% CI: 194–287) µmol/L compared to pair-fed controls 29 (95% CI: 26–32) µmol/L. Repletion of potassium normalized the changes. CONCLUSIONS: Hypokalemia markedly increased plasma ammonia concentrations. The capacity for urea synthesis was impaired, but only moderately so, and further studies are needed to fully explain the causes of hyperammonemia.