Postnatal development of the actual and total activity of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues

Veerkamp, J.H.; Wagenmakers, Anton J. M.

doi:10.1016/0020-711x(87)90334-x

Cited by 4 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported [46] that the liver BCKDC activity increases in rat pups throughout the suckling period, reaching adult levels at the age of weaning (21 days). In addition, total BCKDC activity in the liver rises during postnatal development (until 30-40 days of age) and then tends to drop at around 60 to 70 days of age [47,48]. To our knowledge, no further information is available regarding age-dependent changes in rat hepatic BCKDC activity after 10 weeks of age; thus, this issue needs further clarification in future studies.…”

Section: Discussionmentioning

confidence: 77%

Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus

Bajotto¹,

Murakami²,

Nagasaki³

et al. 2009

Metabolism

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 77%

Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus

Bajotto¹,

Murakami²,

Nagasaki³

et al. 2009

Metabolism

View full text Add to dashboard Cite

“…An age-dependent increase in BCODC activity during neonatal development of the rat has been documented previously by others [9][10][11]. The work of May et al [9] first described the developmental pattern for the liver, but whether the increase throughout the suckling period was due to a change in enzyme mass or covalent modification was not investigated.…”

Section: Discussionmentioning

confidence: 83%

“…The work of May et al [9] first described the developmental pattern for the liver, but whether the increase throughout the suckling period was due to a change in enzyme mass or covalent modification was not investigated. Veerkamp et al [10] and Grogan et al [11] measured enzyme activity by a flux method [32] and concluded that the hepatic enzyme was largely in its active, dephosphorylated form throughout postnatal development. The present work further documents the increase in hepatic enzyme activity throughout the suckling period of development and confirms that the increase in enzyme activity in the liver is due to an increase in expressed amount of BCODC subunits rather than a change in activity (phosphorylation) state of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Newborn human infants, as well as newborn calves with classic MSUD, appear normal at birth but rapidly develop a severe neurological disorder, indicating that a functional BCODC must be either present at birth or induced within a few days of birth in humans and cattle in order to avoid the consequence of failure to dispose of excessive amounts of BCAA [6,8]. In this regard, it is surprising that previous developmental studies of BCODC in the rat have indicated very low activity at birth and a relatively slow increase in activity during the suckling period [9][10][11]. Since the latter work was levels for the liver Ela, E1,/, and E2 subunits in newborn rat were 300%, 190%, and 40% of adult levels respectively.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Developmental pattern of branched-chain 2-oxo acid dehydrogenase complex in rat liver and heart

Zhao

Denne

Harris

1993

Biochemical Journal

View full text Add to dashboard Cite

The developmental pattern of the branched-chain 2-oxo acid dehydrogenase complex was examined in the liver and heart of the rat throughout the suckling period. Basal activity and total activity of the complex were measured as a function of age. The hepatic enzyme activity increased dramatically and was 100% active (dephosphorylated) during the suckling period. The level of protein kinase associated with the complex was particularly low at birth, but like the complex increased throughout the suckling period. The level of heart enzyme also increased as a function of age, but only about 30-45% of the enzyme was active throughout the suckling period. Very low protein levels of liver and heart branched-chain 2-oxo acid dehydrogenase were detected by immunoblot analysis in newborn rats. The mRNA levels for the liver E1 alpha, E1 beta, and E2 subunits in newborn rat were 30%, 19%, and 4% of adult levels respectively. The capacity of the neonatal rat for oxidizing leucine in vivo was low at birth and increased with age. 4-Methyl-2-oxopentanoate was more toxic when given to newborn and 3-day-old pups than 21-day-old pups, as expected from the relative capacities of their tissues to dispose of branched-chain 2-oxo acids by oxidation. Force-feeding suckling rats a protein-free artificial milk formula resulted in partial inactivation of the hepatic branched-chain 2-oxo acid dehydrogenase complex, indicating that the liver of the suckling rat can adapt to conserve branched-chain amino acid residues during periods of protein deficiency.

show abstract

“…Previous studies have reported hepatic BCKAD activity states of nearly 100% in neonatal rat pups Ͻ12 h old (39,40). However, our study focuses on fetal rat pups, which differ from neonatal rat pups in several ways.…”

Section: Liver and Muscle Bckad In Iugr Fetal Ratsmentioning

confidence: 99%

Uteroplacental Insufficiency Alters Liver and Skeletal Muscle Branched-Chain Amino Acid Metabolism in Intrauterine Growth-Restricted Fetal Rats

et al. 2001

View full text Add to dashboard Cite

Uteroplacental insufficiency causes intrauterine growth restriction (IUGR) and decreases plasma levels of the branchedchain amino acids in both humans and rats. Increased fetal oxidation of these amino acids may contribute to their decline in the IUGR fetus. The rate-limiting step of branched-chain amino acid oxidation is performed by the mitochondrial enzyme branched-chain ␣-keto acid dehydrogenase (BCKAD), which is regulated by a deactivating kinase. We therefore hypothesized that uteroplacental insufficiency increases BCKAD activity through altered mRNA and protein levels of BCKAD and/or the BCKAD kinase. In IUGR fetal liver, BCKAD activity was increased 3-fold, though no difference in hepatic BCKAD protein or mRNA levels were noted. Hepatic BCKAD kinase mRNA and protein levels were significantly decreased in association with the increase in BCKAD activity. In IUGR fetal skeletal muscle, BCKAD mRNA levels were significantly increased. IUGR skeletal muscle BCKAD protein levels as well as BCKAD kinase mRNA and protein levels were unchanged. We also quantified mRNA levels of two amino acid transporters: LAT1 (system L) and rBAT (cysteine and dibasic amino acids). Both hepatic and muscle LAT1 mRNA levels were significantly increased in the IUGR fetus. We conclude that uteroplacental insufficiency significantly increases hepatic BCKAD activity in association with significantly decreased mRNA and protein levels of the deactivating kinase. We speculate that these changes contribute to the decreased serum levels of branched-chain amino acids seen in the IUGR fetus and may be an adaptation to the deprived milieu associated with uteroplacental insufficiency. Uteroplacental insufficiency is a common and serious complication of pregnancy. It impairs the exchange of metabolites and gases between the mother and fetus, resulting in IUGR. In humans, the metabolic aberrations associated with the IUGR intrauterine milieu include decreased plasma concentrations of the BCAA: leucine, isoleucine, and valine (1-3). Similarly, Ogata et al. (4) found that uteroplacental insufficiency decreased serum BCAA levels in the IUGR fetal rat. Although decreased supply of the BCAA from the placenta contributes to the low plasma levels noted in the IUGR fetus, increased fetal utilization through increased mitochondrial oxidation may also play a role (5). Several investigators have noted that deprivation of the fetal sheep results in decreased serum levels of leucine and increased fetal leucine oxidation (6 -8).Irreversible oxidative decarboxylation of the BCAA is performed by the mitochondrial enzyme BCKAD (9). BCKAD is an enzyme complex composed of four subunits: E1␣, E1␤, E2, and E3. Whereas the first three subunits are specific for BCKAD, the E3 subunit is common among the three keto-acid dehydrogenase complexes (BCKAD, pyruvate dehydrogenase, and ␣-ketoglutarate dehydrogenase). BCKAD activity often correlates with mRNA and protein levels, though covalent modification through phosphorylation and dephosphorylation of the E1␣ subunit determi...

show abstract

Postnatal development of the actual and total activity of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues

Cited by 4 publications

References 25 publications

Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus

Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus

Developmental pattern of branched-chain 2-oxo acid dehydrogenase complex in rat liver and heart

Uteroplacental Insufficiency Alters Liver and Skeletal Muscle Branched-Chain Amino Acid Metabolism in Intrauterine Growth-Restricted Fetal Rats

Contact Info

Product

Resources

About