Impact of Nutrition on Postnatal Development of Serine-Threonine Dehydratase and Branched-Chain Keto Acid Dehydrogenase in the Rat

Abstract

The developmental patterns of two amino acid-catabolizing enzymes, serine-threonine dehydratase (STD) and branched-chain α-keto acid dehydrogenase (BCKAD), were investigated in growing rats. At 10, 15, 20, 30, and 60 days of age, STD and BCKAD activities were determined in pup tissues. Hepatic STD activity increased more than 3-fold between 10 and 20 days of age; after this peak, activity decreased by 30 days of age. Threonine dosing did not affect STD activity at any age. In the liver, kidney, brain and skeletal muscle, total BCKAD activity increased 2- to 4-fold between 10 and 30 days of age. Percentages of BCKAD active in all tissues decreased between 10 and 15 days of age, associated with a large increase in total activity. The percentages of BCKAD activity were unchanged between 20 and 30 days of age but increased from 30 to 60 days of age, associated with a decrease in total activity. Leucine dosing did not affect total BCKAD activity at any age. These results demonstrate that both STD and BCKAD develop late during the suckling period and total activities are unresponsive to excess dietary amino acids.

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

“…Similar results on heart actual and total activities were described by Veerkamp et al [10]. Grogan et al [11] reported similar results for the skeletal muscle and brain for 10-day-old to 30-day-old suckling rats. The proportion of the heart enzyme that was dephosphorylated and active was greater during the suckling period than observed with the heart enzyme of mature animals [12,19].…”

“…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.…”

“…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.…”

“…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.…”

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

“…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.…”