scholarly journals Development of gluconeogenesis in neonatal rat liver. Effect of premature delivery

1967 ◽  
Vol 105 (3) ◽  
pp. 1229-1233 ◽  
Author(s):  
D. Yeung ◽  
I. T. Oliver

1. An assay method for the determination of phosphopyruvate carboxylase activity is described in which improved sensitivity is obtained by separation of the enzyme from interfering pyruvate kinase by zone sedimentation. 2. The molecular weight of rat liver phosphopyruvate carboxylase determined by zone sedimentation is about 68000. 3. Premature delivery of rat foetuses by uterine section results in the rapid appearance of phosphopyruvate carboxylase, but hexose diphosphatase and pyruvate carboxylase, already present in the foetal rat liver, are not significantly affected, and glucose 6-phosphatase activity is only slightly affected. 4. The rate of incorporation of [14C]pyruvate into glucose by liver slices is also greatly increased by premature delivery and there is a highly significant linear correlation between this process and the phosphopyruvate carboxylase activity.

1967 ◽  
Vol 105 (3) ◽  
pp. 1219-1227 ◽  
Author(s):  
D. Yeung ◽  
R. S. Stanley ◽  
I. T. Oliver

1. The normal development of the key enzymes of gluconeogenesis in rat liver, glucose 6-phosphatase, hexose diphosphatase, phosphopyruvate carboxylase and pyruvate carboxylase, was measured during the neonatal period. 2. Glucose 6-phosphatase, hexose diphosphatase and pyruvate carboxylase are all present in the late foetal liver, but all the enzymes show an increase in activity after birth. 3. Phosphopyruvate carboxylase is not present in liver extracts from foetal rats, but activity appears immediately after birth and increases rapidly over the first day and then more slowly to reach its maximum at the fourth postnatal day. 4. The fluorinated synthetic glucocorticoid, triamcinolone, was administered to foetal rats at various gestation times by intraperitoneal injection in utero and the animals were killed at intervals between 4 and 48hr. later. 5. The administration of triamcinolone results in slight depression of glucose 6-phosphatase, and a more significant depression of hexose diphosphatase to about one-half its normal activity in foetal rat liver. 6. Triamcinolone injection is without effect on pyruvate carboxylase activity and does not result in premature appearance of phosphopyruvate carboxylase in foetal rat liver. 7. Pyruvate kinase and aspartate amino-transferase activities in foetal rat liver are both depressed by triamcinolone treatment, whereas phosphofructokinase activity is elevated. 8. Tyrosine amino-transferase activity in foetal rat liver is markedly elevated in animals exposed to triamcinolone for 10hr. or more, but the effect is only observed in animals close to term. 9. The results are discussed in relation to mechanisms involved in the initial synthesis of tissue-specific enzymes in developing tissues, and it is concluded that glucocorticoids do not initiate the synthesis of the gluconeogenic enzymes.


1975 ◽  
Vol 150 (3) ◽  
pp. 477-488 ◽  
Author(s):  
J K Pollak

A new method was devised for the isolation of foetal and neonatal rat lvier mitochondria, giving higher yields than conventional methods. 2. During development from the perinatal period to the mature adult, the ratio of cytochrome oxidase/succinate-cytochrome c reductase changes. 3. The inner mitochondrial membrane of foetal liver mitochondria possesses virtually no osmotic activity; the permeability to sucrose decreases with increasing developmental age. 4. Foetal rat liver mitochondria possess only marginal respiratory control and do not maintain Ca2+-induced respiration; they also swell in respiratory-control medium in the absence of substrate. ATP enhances respiratory control and prevents swelling, adenylyl imidodiphosphate, ATP+atractyloside enhance the R.C.I. (respiratory control index), Ca2+-induced respiratory control and prevent swelling, whereas GTP and low concentrations of ADP have none of these actions. It is concluded that the effect of ATP depends on steric interaction with the inner mitochondrial membrane. 5. When 1-day pre-partum foetuses are obtained by Caesarean section and maintained in a Humidicrib for 90 min, mitochondrial maturation is ‘triggered’, so that their R.C.I. is enhanced and no ATP is required to support Ca2+-dependent respiratory control or to inhibit mitochondrial swelling. 6. It is concluded that foetal rat liver mitochondria in utero do not respire, although they are capable of oxidative phosphorylation in spite of their low R.C.I. The different environmental conditions which the neonatal rat encounters ex utero enable the hepatic mitochondria to produce ATP, which interacts with the inner mitochondrial membrane to enhance oxidative phosphorylation by an autocatalytic mechanism.


1979 ◽  
Vol 182 (1) ◽  
pp. 233-235 ◽  
Author(s):  
J E A Leakey ◽  
J R Fouts

Intraperitoneal injection of neonatal rats with glucocorticoid hormones causes precocious development of hepatic cytochrome P-450. Glucagon injection fails to stimulate this cytochrome P-450 development. Adult liver cytochrome P-450 is less responsive to glucocorticoid stimulation than is that of neonatal rat liver. Adrenalectomy of prematurely delivered neonatal animals prevents the early postnatal development of cytochrome P-450. Glucocorticoids failed to increase cytochrome P-450 concentrations in foetal rat liver. These findings imply that, although glucocorticoids are mandatory regulatory factors controlling cytochrome P-450 development, they are not themselves the ‘trigger’ initiating onset of that development.


1972 ◽  
Vol 127 (4) ◽  
pp. 721-731 ◽  
Author(s):  
Marshall C. Middleton ◽  
Deryck G. Walker

1. Two forms of hepatic pyruvate kinase, designated type L and type M, were distinguished on the basis of kinetic, chromatographic, electrophoretic and immunological criteria. They were partially purified and their properties compared with each other and with the purified enzyme from skeletal muscle. 2. In contrast with type L, the type M enzyme showed no marked evidence of co-operative interactions with phosphoenolpyruvate and was not stimulated by fructose diphosphate. 3. The activity profiles of type L and type M enzymes were determined in developing rat liver by utilizing differences in the kinetic properties of the two forms. The high activity of type M enzyme in the early foetal rat decreased in late gestation and immediately after birth to reach a low value, which remained essentially constant for the remainder of the developmental period. The activity of type L enzyme, in contrast, was low in the early foetal and neonatal liver but increased markedly at the onset of weaning. 4. Possible roles of the two forms of hepatic pyruvate kinase in the control of glycolysis and gluconeogenesis are discussed.


1968 ◽  
Vol 108 (2) ◽  
pp. 325-331 ◽  
Author(s):  
D. Yeung ◽  
I. T. Oliver

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.


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