Enzymatic and Metabolic Studies on Carbohydrate and Amino Acid Metabolism in Rat Liver during Acute Uraemia

Abstract

Abstract. Enzyme activities of the glycolytic, gluconeogenic, and hexose monophosphate pathways were measured in the liver of starved rats 12 and 48 hours after bilateral nephrectomy. Control experiments (sham operated rats) revealed that alterations of enzyme activities were not due to uraemia but to starvation. Alanine‐aminotransferase and aspartate‐ aminotransferase activities, however, were significantly elevated in rat liver 48 hours after nephrectomy when compared with sham operated controls. Concentrations of some of the gluconeogenic intermediates (3‐phosphoglyceric acid, pyruvate, phosphoenolpyruvate and glucose‐6‐phosphate) were significantly higher in the liver of uraemic animals. Amino acid analysis showed an increase in only L‐alanine concentration. It is suggested that the elevated content of pyruvate in the liver during acute uraemia is due to an inhibition of pyruvate degradation. Together with the elevated pyruvate concentration the increase in L‐alanine could be explained as a consequence of the equilibrium of the alanine‐aminotransferase reaction; Kapp. of the reaction is not changed by uraemia. Increased activities of the transaminases and the elevated concentrations of the other metabolites measured might indicate that in the liver of nephrectomized rats there is enhanced gluconeogenesis from substrates other than pyruvate.

The Gluconeogenetic Ability of Hepatocytes in Various Types of Acute Uraemia

“…In the uraemic groups in which an increased gluconeogenesis from serine was ob served, increases in pyruvate and lactate production were also shown. These data cannot exclude the possibility that stimulation of glucose production from serine was due to enhanced transport of amino acids into the liver cells [8,9,19,20] or higher activity of liver transaminases in uraemia [21].…”

“…Maier et al [21] have shown unchanged activity of FDPase in the liver of binephrectomised rats. A signifi cant dependency between the rate of gluconeogenesis and the medium pH value suggests that glucose-6-phosphatase is the rate-limiting step.…”

Skeletal Muscle Protein and Amino Acid Metabolism in Experimental Chronic Uremia in the Rat

“…As shown in Table I, levels of ATP, ADP, and phosphocreatine in epitrochlearis preparations, which were freeze-clamped in situ, were not significantly An increased rate of release of most of the amino acids studied was found on incubation of skeletal muscle preparations from chronically uremic rats (Table II). With uremic muscle, alanine release was increased 46.8% (P < 0.01), aspartate release was in- creased 200% (P < 0.05), glutamate release was increased 61.5% (P < 0.02), glutamine release was increased 36.0% (P < 0.02), and total amino acid release was increased 42.0% (P < 0.02). Although rates of muscle alanine and glutamine release were increased in uremia, tissue levels of these two amino acids were not altered in uremic animals as compared with control animals (Table II).…”

“…Alanine and glutamine account for the bulk of amino acids released by muscle (21). Studies performed in vitro using an isolated perfused liver model for hepatic gluconeogenesis have demonstrated that uremia is associated with an increased maximal capacity for hepatic glucose production from amino acids (42,43). Because studies performed in vivo as well as in vitro have demonstrated that the rate of alanine delivery can be rate limiting for gluconeogenesis (7,44), the findings of the present study demonstrating an increased rate of alanine production and release from skeletal muscle in uremia, suggest that an increased rate of hepatic gluconeogenesis from alanine may indeed occur in vivo.…”

Glycogen Synthesis from Serine in Isolated Perfused Hindquarters of Acutely Uraemic Rats

“…Disturbances of carbohydrate metabolism in acute uraemia are influenced by the degradation of liver and muscle glycogen as well as activation of hepatic gluconeogenesis [1][2][3][4][5][6][7][8]. Fröhlich et al [2,3] found a stimulation of gluconeogenesis in the presence of amino acids in liver per fusion experiments in acutely uraemic rats.…”