Increase In Phosphoenolpyruvate Carboxykinase Activity Research Articles

Metabolic adaptation in muscle of phosphorylase deficiency (McArdle's disease)?

In a case of McArdle's disease (muscle phosphorylase deficiency) enzyme activities of glycogen metabolism, glycolysis and phosphoenolpyruvate metabolism were measured. Besides the deficiency of muscle phosphorylase, a marked increase in phosphoenolpyruvate carboxykinase activity was found in the muscle investigated. The increase in phosphoenolpyruvate carboxykinase activity is regarded as an adaptive mechanism providing phosphorylated intermediates for energy supply to the muscle.

The development of gluconeogenesis in rat liver. Controlling factors in the newborn.

1. Measurements in livers of rats delivered by Caesarian section show a rapid change in the relative proportion of adenine nucleotides. By 20min the ATP/ADP ratio had increased from 1.76 to 8.7 and the value of the relationship [ATP][AMP]/[ADP](2) increased from 1.0 to 4.4. These changes are dependent on the availability of oxygen to the animal. 2. The free [NAD(+)]/[NADH] ratio in the liver cytosol increases from 180 after delivery to reach a maximum of 1010 at 2h, before falling to 540 in the 24h-old animal. 3. The mitochondrial NAD redox potential also shows a sharp increase towards a more oxidized state in livers of delivered rats. 4. These results probably indicate that the foetal liver is hypoxic, with oxygenation occurring in the first hour after delivery. 5. Measurements in livers of naturally born rats 2min after birth also suggest that this tissue is hypoxic with an ATP/ADP ratio of 1.83 and a free [NAD(+)]/[NADH] ratio of 117. 6. Concentrations of intermediates in the gluconeogenic pathway have been determined in livers of foetal, 1h-old and 1-day-old rats. These experiments imply a facilitation of lactate dehydrogenase and glucose 6-phosphatase activities by 1h after birth, and a stimulation of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase steps by 1 day after birth. 7. The appearance of gluconeogenesis in livers of newborn rats seems therefore to involve an oxygenation stage followed by an increase in phosphoenolpyruvate carboxykinase activity.

Glyceroneogenesis in adipose tissue of fasted, diabetic and triamcinolone treated rats.

Incorporation of [2-14C]pyruvate into adipose tissue triglycerides was measured in fasted, diabetic and triamcinolone treated rats and related to the activity of enzymes active in the elaboration of glyceride glycerol. Incorporation of pyruvate into glyceride glycerol was increased in fasting and diabetes. The activity of phosphoenolpyruvate carboxykinase increased in parallel with the enhanced glyceroneogenesis, whereas the activity of pyruvate carboxylase changed in the opposite direction. After triamcinolone treatment, the activity of both enzymes was decreased as was the incorporation of [2-14C]pyruvate into glyceride glycerol. In all experimental animals glutamate-pyruvate transaminase activity in adipose tissue decreased, whereas the activity of glutamate-oxaloacetate transaminase increased slightly. These results were interpreted as implying that the enhanced glyceroneogenesis in diabetes and fasting is related to the increase in phosphoenolpyruvate carboxykinase activity, whereas pyruvate carboxylase activity seems associated with changes in fatty acid synthesis. In contrast to adipose tissue, in the liver the activity of both enzymes of the dicarboxylic acid shuttle and of transaminases increased in the situations associated with enhanced gluconeogenesis. This finding is discussed in the light of possible differences in the availability of precursors for gluco- and glyceroneogenesis in the respective tissues. The role of glyceroneogenesis is pointed out, as one of the factors maintaining the balance between synthesis and breakdown of triglycerides in adipose tissue, particularly in conditions associated with rapid lipolysis.

Renal metabolic response to acid base changes. I. Enzymatic control of ammoniagenesis in the rat.

Experiments were done on rats to investigate the nature of the renal response to metabolic acidosis and the changes in enzyme activity associated with increased ammoniagenesis. When metabolic acidosis was induced with oral feeding of ammonium chloride for 48 hr, there was an increase of activity of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) in whole kidneys as well as in the kidney cortex. There was no change in PEPCK in liver, and glucose-6-phosphatase showed no change in kidney or liver in response to metabolic acidosis. The increase in PEPCK activity in kidney cortex varied with the degree of acidosis and there was a close correlation between cortical PEPCK activity and urinary ammonia. Kidney cortex mitochondrial PEPCK did not change in response to metabolic acidosis. An increase in PEPCK occurred as early as 6 hr after NH(4)Cl feeding, before there was any increase in kidney glutaminase I activity. Rats fed sodium phosphate, or given triamcinolone intramuscularly, developed a metabolic alkalosis, but there was increased urinary ammonia and an increase in activity of renal cortical PEPCK. Triamcinolone plus ammonium chloride induced a greater increase of PEPCK activity than triamcinolone by itself; on the contrary, the rise of glucose-6-phosphatase induced by triamcinolone was not enhanced by acidosis. Glucose-6-phosphatase from control and acidotic rats had identical kinetic characteristics. The results indicate that increased PEPCK activity is constantly related to increases of urinary ammonia. It is proposed that the increase of PEPCK activity is the key event in the ammoniagenesis and gluconeogenesis which follow on metabolic acidosis.