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

Abstract

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)

Substrate Utilization and Brain Development

“…The estimated rates of oxidative metabolism of glucose and ketone bodies obtained by Cremer and Heath (1974) agreed very closely with rates calcu lated by Dahlquist and Persson (1976) from ar teriovenous differences, and confirm that ketone bodies can account for at least 30% of the total in suckling rats.…”

“…The suggestion made above that the carrier was a major determinant of the rate at which ketone bodies were metabolized by the infant rat brain was based on the closeness of estimated rates of uni directional and net influx. On the basis of measured blood concentrations of o-3-hydroxybutyrate and acetoacetate in suckling rats and the V max and Krn values for the brain enzymes o-3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA-transferase, Cremer and Heath (1974) argued that the capacity of the enzymes was several times greater than the ac tual rate through these enzymic steps in vivo. They suggested that entry of ketone bodies into brain was restricted, even in suckling rats, and that metabo lism was substrate-limited.…”

“…Rates of utilization of glucose and ketone bodies in the whole brain of 18-day-old rats using com partmental analysis of isotopic data were deter mined by Cremer and Heath (1974). Rates of whole brain glucose metabolism have also been deter mined by Miller and Corddry (1981) using [2_14C] glucose and 2-[3H]deoxyglucose, and a comparison was made between 10-and 20-day-old animals.…”

“…In their studies in the infant rat, Cremer and Heath (1974) noted a large loss of label from the brain in products formed from 2-[14C]glucose. This was shown to be due to the rapid movement of lactate and pyruvate between the brain and blood.…”

“…These investigators used the glucose analogue 2-[3H]deoxyglucose and estimated CMRglu values of 19 /Lmol 100 g-l min-1 for the 1O-day-old rat brain and 53 /Lmol 100 g-l min-1 for the 20-day old rat brain. Cremer and Heath (1974) measured the time course for incorporation of label from substrates entering the brain into intermediary metabolites, in cluding the amino acids. Results seemed to indicate that glucose, lactate, pyruvate, and ketone bodies labeled identical pools of tricarboxylate-cycle me tabolites.…”