Regulation of the rate of urea synthesis in liver by extracellular pH. A major factor in pH homeostasis in mammals.

E S Bean,D E Atkinson

doi:10.1016/s0021-9258(17)43444-2

Abstract

The views that catabolism of protein leads to net production of acid and that urinary excretion of ammonium ion represents an equimolar excretion of proton are not compatible with basic chemical relationships (Atkinson, D.E., and Camien, M.N. (1982) Curr. Top. Cell. Regul. 21, 261-302). Metabolism of protein produces significant amounts of base (bicarbonate), which is disposed of in the synthesis of urea. In perfused rat liver and in isolated rat hepatocytes, the rate of urea synthesis increases with increase in pH but is not affected by change in the concentration of bicarbonate when pH is held constant. An increase in the concentration of ammonium ion in the suspending medium causes an increase in the rate of urea synthesis by hepatocytes when lactate is the energy source, as previously reported by others, but causes a decrease in the rate of urea synthesis during incubation with glucose or with no added energy source. The rate of urea synthesis decreases when glucose is added to lactate medium. All of these observations are consistent with the view that disposal of bicarbonate is a major function of urea synthesis, and that regulation of the rate of ureagenesis is an important factor in the maintenance of pH homeostasis.

Highlights

C02-When the pHof the medium perfusing theliver from a fed rat was changed from7.0 to 7.6 by increasing theconcentration of bicarbonate, while holding theconcentration of carbon dioxide at its physiological value of 1.2 mM, the rate of urea synthesis increased by 50%, rising from 440 to 660 nmol/min/g wet weight in about 30 min (Fig. 1).When the initial medium was restored, the rate of urea synthesis returned to its formevralue with about the same time constant
In hepatocytes suspended in media that contained lactate as the carbon and energy source, the rate of urea synthesis
To 1.0 mM, was in the opposite direction: an increase in the Our results are consistent with tvhiew that urea synthesis concentration of ammonium ioncaused a decrease in the rate serves primarily todispose of bicarbonate and maintain of urea synthesis

Summary

Introduction

Effect of NH: concentration and carbon source on the rate of base of the major extracellular buffer system in vertebrates, synthesis of urea its concentration must be regulated if pH stability is to be Hepatocytes (2.1 mg) isolated from the liver of a fasted rat were maintained.

Results

Conclusion