The activity of pyruvate dehydrogenase in rat brain during postnatal development

Cremer, Jill E.; Teal, Hazel M.

doi:10.1016/0014-5793(74)80006-2

Cited by 89 publications

(39 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). This result, together with the presence of low NADH levels, is consistent with a high requirement for NADPH for biosynthetic processes associated with the rapid growth phase in neonatal rat liver during early development (1,14) and a limited oxidation of NADH (8,10,23). It is possible that the differences in pyridine nucleotide composition and distribution can be attributed, in part, to contribution from nonparenchymal and hematopoietic cells, which constitute a relatively large percentage, by mass, of the liver of newborn rats (1).…”

Section: Discussionsupporting

confidence: 75%

“…These results suggest that oxidation of NADH is limited during the late fetal and early perinatal phases of development (8). The relatively slower ontogenic development of pyruvate dehydrogenase activity compared to other mitochondrial enzymes (9) is consistent with a limited utilization of glucose or lactate for energy production (8,10). Together, the limitation of NADf-linked oxidations and the selective oxidation of succinate as an alternate fuel in neonatal cells would spare NADH to supply NADPH for enhanced biosynthetic processes that are associated with increased tissue growth during this period.…”

mentioning

confidence: 87%

See 1 more Smart Citation

Postnatal Changes in Pyridine Nucleotides in Rat Hepatocytes: Composition and O2 Dependence

1991

Pediatr Res

View full text Add to dashboard Cite

ABSTRACT. Postnatal changes in pyridine nucleotide concentration, composition, and oxidation-reduction characteristics were studied in liver cells from neonatal (newborn, d 4 and d 8) and adult rats to determine the development of hepatic pyridine nucleotide status and O2 dependence of oxidation of reducing equivalents. The results show that the total pyridine nucleotide concentrations in newborn and 4-d-old rat liver were low (30%) but increased to near adult values (80%) by d 8 postpartum. Analyses of the cellular distribution of NAD+, NADH, NADP", and NADPH reveal that the reduced forms (NADH plus NADPH) accounted for over 50% of the total in the newborn and 4-dold rats compared to 30% in adult animals. This relatively higher reductive capacity in hepatocytes of younger rats was largely the result of a significantly higher proportion of NADPH in these cells. Examination of the NADPH/ NADP+ and NADH/NAD+ ratios show that they occur in an inverse relationship with postnatal age; the NADPH/ NADPC ratio was high at birth and decreased with age, whereas the reverse pattern was found for the NADH/ NAD+ ratio. The result, that NADPH represents a significant percentage of the total pyridine nucleotides in neonatal cells in the early postnatal period, is consistent with a higher demand for NADPh for biosynthetic activities in association with tissue growth. A high NADPH concentration coupled with a low NADH concentration in these cells is further consistent with the finding that succinate is a preferred substrate for newborn respiratory function so as to spare NADH for transhydrogenation to NADPH. The half-maximal oxidation of pyridine nucleotides in cells from newborn rats occurred at 0.49 pM 0 2 , as compared to 1.2 and 4.0 pM O2 in cells from 4-d-old and adult rats, respectively. Direct comparison of the Oz dependencies of pyridine nucleotides at different ages with those of cytochrome c + el demonstrates that the oxidation of pyridine nucleotides occurs in concert with the expression of mitochondrial respiratory components during development. (Pediatr Res 30: 11 2-1 17, 1991) Abbreviations PS0, half-maximal associated greater demand for oxidizable substrates and reducing equivalents. In liver, the age-dependent increase in cellular respiration is attained by marked changes in the composition and contents of the enzymes of the respiratory systems (1-5) and by selective use of specific respiratory substrates (6, 7). We recently found that hepatocytes from newborn rats preferentially use succinate for cell respiration compared to a variety of other carbohydrate or amino acid substrates (6,7). These results suggest that oxidation of NADH is limited during the late fetal and early perinatal phases of development (8). The relatively slower ontogenic development of pyruvate dehydrogenase activity compared to other mitochondrial enzymes (9) is consistent with a limited utilization of glucose or lactate for energy production (8, 10). Together, the limitation of NADf-linked oxidations and the selective oxidation of succin...

show abstract

Section: Discussionsupporting

confidence: 75%

mentioning

confidence: 87%

Postnatal Changes in Pyridine Nucleotides in Rat Hepatocytes: Composition and O2 Dependence

1991

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…Flux through the step pyruvate to acetyl-CoA was estimated to be betweenO.51 and 0.93 ,umol/min per g and these values were remarkably close to those obtained for the total activity of pyruvate dehydrogenase in the 18-day-old rat brain (Cremer & Teal, 1974). If assays of pyruvate dehydrogenase in vitro do indeed reflect the activity of the enzyme in situ then the results would imply that the capacity of the young rat brain to oxidize carbohydrate is strictly limited.…”

Section: Regulation Ofenzymessupporting

confidence: 82%

The estimation of rates of utilization of glucose and ketone bodies in the brain of the suckling rat using compartmental analysis of isotopic data

Cremer

Heath

1974

Biochemical Journal

133

View full text Add to dashboard Cite

The brains of 18-day-old rats utilize glucose and ketone bodies. The rates of acetyl-CoA formation from these substrates and of glycolysis were determined in vivo from the labelling of intermediary metabolites after intraperitoneal injection of D- [2-'4C] (1971) showed by arterio-venous difference measurements across the brain that the other substrates were predominantly the ketone bodies, acetoacetate and 3-hydroxybutyrate. They determined relative oxidation rates of glucose and the ketone bodies, but absolute rates could not be determined because the rate of blood flow in the brain was not known.We decided to determine the rates of utilization of these substrates by using a method that does not require a knowledge of blood flow, but is based on the retention of label in brain after intraperitoneal injection of substrates labelled with "4C. The method was applied to conscious rats at an age, 18 days, when all three substrates were known to be utilized by the brain.Earlier studies had shown that 14C entering the brain either as glucose (Cremer, 1964;Gaitonde, 1965)

show abstract

“…Changes in activity of pyruvate dehydrogenase in rat brain from birth to adulthood have been deter mined in several studies (Cremer and Teal, 1974;Wilbur and Patel, 1974;Stumpf and Kraus, 1979;Booth et aI., 1980). Activity is very low during the first week, then rises rapidly between 10 and 30 days of age and is highest in the adult.…”

Section: Ratsmentioning

confidence: 99%

“…Activity is very low during the first week, then rises rapidly between 10 and 30 days of age and is highest in the adult. The differ ence between the activities in the newborn and adult is about 10-fold with V max values of 0.2 and 2.0 /Lmol g-l min-t, respectively, for the activated form of the enzyme (Cremer and Teal, 1974;Booth et aI., 1980). A consistent finding of arteriovenous difference measurements in suckling rats has been net output of lactate from brain to blood whenever ketone bodies were metabolized by the brain (Hawkins et aI., 1971;Dahlquist and Persson, 1976).…”

Section: Ratsmentioning

confidence: 99%

Substrate Utilization and Brain Development

Cremer

1982

J Cereb Blood Flow Metab

167

View full text Add to dashboard Cite

The activity of pyruvate dehydrogenase in rat brain during postnatal development

Cited by 89 publications

References 19 publications

Postnatal Changes in Pyridine Nucleotides in Rat Hepatocytes: Composition and O2 Dependence

Postnatal Changes in Pyridine Nucleotides in Rat Hepatocytes: Composition and O2 Dependence

The estimation of rates of utilization of glucose and ketone bodies in the brain of the suckling rat using compartmental analysis of isotopic data

Substrate Utilization and Brain Development

Contact Info

Product

Resources

About