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Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver
Insights
Neonatal rat liver enzyme synthesis, specifically phosphopyruvate carboxylase, is triggered by hormones like glucagon and adrenaline, but repressed by glucose and other metabolites.
Area of Science:
- Biochemistry
- Developmental Biology
- Neonatal Physiology
Background:
- Premature delivery in rats is associated with a transient hypoglycemic phase.
- Phosphopyruvate carboxylase activity is crucial for gluconeogenesis in the liver.
Purpose of the Study:
- To investigate the factors regulating the rapid appearance of phosphopyruvate carboxylase activity in the neonatal rat liver.
- To elucidate the mechanism of initiation of enzyme synthesis post-delivery.
Main Methods:
- Studied the effect of various injections (actinomycin D, puromycin, glucose, galactose, lactate, pyruvate, glycerol, glucagon, adrenaline, noradrenaline) on enzyme activity in prematurely delivered rats.
- Assessed enzyme synthesis by observing the impact of protein synthesis inhibitors.
Main Results:
- Phosphopyruvate carboxylase activity development is prevented by actinomycin D, indicating de novo enzyme synthesis.
- Inhibitors of protein synthesis (puromycin, amino acid analogues) decrease activity.
- Glucose injection preventing hypoglycemia also represses enzyme development, as do other sugars and metabolites.
- Hormonal stimulation (glucagon, adrenaline, noradrenaline) in utero promotes enzyme activity.
Conclusions:
- Neonatal phosphopyruvate carboxylase activity is regulated by both substrate availability and hormonal signals.
- Enzyme synthesis is initiated by hormonal cues and modulated by metabolic conditions post-delivery.
Abstract:
1. Phosphopyruvate carboxylase activity rapidly appears in the liver of prematurely delivered rats and development of activity is prevented by injection of actinomycin D just before delivery. 2. The activity is considerably decreased by puromycin and amino acid analogues and thus appears to be due to enzyme synthesis. 3. Newborn or premature animals show a transient intense phase of hypoglycaemia after delivery. 4. When the hypoglycaemic phase is prevented by glucose injection little phosphopyruvate carboxylase activity appears in the liver, but galactose, mannose and fructose, which have no effect on the blood glucose concentration, also repress enzyme development. 5. Lactate, pyruvate and glycerol injections repress the premature development of phosphopyruvate carboxylase. 6. Injections of glucagon, adrenalin and noradrenalin into the rat foetus in utero result in development of phosphopyruvate carboxylase activity. 7. These findings are discussed in relation to the mechanism of initiation of enzyme synthesis in neonatal rat liver.