Restriction of hepatic gluconeogenesis and ureogenesis from threonine when at low concentrations

Abstract

Experiments were carried out with the isolated perfused liver of the overnight-starved rat to study the control of the conversion of the essential amino acid threonine to glucose and urea from the point of view of its conservation when in short supply. The relationships between the concentration of added L-threonine and the rate of glucose and urea production showed that both pathways have considerable capacity and were saturated at a high (15 mM) concentration of threonine. However, these concentration-rate relationships were sigmoidal, so that at low concentrations the rates of conversion were disproportionately low. Thus at physiologic levels of threonine, no measurable stimulation of glucose or urea output was observed. Hepatic uptake of threonine was similarly disproportionately reduced at near-physiologic levels. Glucagon stimulated glucose and urea outputs in parallel fashion and stimulated the uptake and inward membrane transport of threonine at both saturating and low concentrations. This and the changes in intracellular and extracellular concentrations of threonine indicate the transport is rate limiting for both pathways. If this is so, the apparent restrictive property probably resides at the plasma membrane. Since the liver is the end point of threonine metabolism, this property would effectively limit the utilization of threonine when in short supply.