D. F. Heath

SOME DYNAMIC ASPECTS OF BRAIN METABOLISM IN RATS GIVEN A PORTOCAVAL ANASTOMOSIS

Some dynamic aspects of brain metabolism in rats given a portocaval anastomosis

The influence of portocaval anastomosis on the metabolism of labelled octanoate, butyrate and leucine in rat brain.

Rats were given a portocaval anastomosis and 3 weeks later, when the only ultrastructural change in the CNS is watery swelling of astrocytes, several aspects of brain metabolism were studied. The uptake of leucine by the brain, its incorporation into protein and its oxidation were followed after the simultaneous injection of a mixture of L‐[114C]leucine and L‐[4,5‐3H]leucine. The concentration of leucine in blood was lowered in the operated animals whereas in brain it was increased. The specific radioactivity of leucine in the brain was comparable to values in control animals and there was no evidence of a decrease in incorporation of [1‐14C]leucine into brain proteins over the short experimental time period studied. The only difference from the controls in the oxidation of [4,5‐3H]leucine was a greater accumulation in glutamine. The amount of glutamine in the brains of the operated animals had increased 4‐fold at the time of the metabolic studies.

An Experimental Model of CNS Changes Associated with Chronic Liver Disease: Portocaval Anastomosis in the Rat

In our summarizing remarks on an earlier discussion of the metabolic compartmentation of glutamate and its associated metabolites in the brain (Balazs and Cremer, 1973), we suggested that more rigorous attempts should be made to test the validity of the compartmentation models put forward at that time. In one of these models (Balazs et al., 1973) it was proposed that glia play a dominant role in the synthesis of glutamine in the brain and that it was these cells that made a major contribution to a so-called metabolic “small” compartment, numbered I in their model. In this compartment the rate of conversion of glutamate to glutamine is high relative to the rate of its oxidation and decarboxylation. Labeled precursors that are indicators of a small-compartment type of metabolism, beacause they give specific radioactivity ratios of glutamine/glutamate > 1.0, include acetate, and leucine.

Glucose and Ketone-Body Utilization in Young Rat Brains: A Compartmental Analysis of Isotopic Data

There have been only a few studies in which rates of glucose and ketone-body metabolism have been estimated in the brains of small, conscious animals. Most of these have used arterio-venous difference measurements, a method that requires a knowledge of the rate of blood flow through the brain, and in small, conscious animals that is difficult to determine. Moreover, the method only gives overall net uptake rates, and no estimates of the rates of the various intermediate steps can be obtained. Results of an alternative approach are described in this chapter, whereby estimates of rates of various intermediary steps of metabolism in the brain were based on a compartmental analysis of isotopic data. Animals were injected with the following labeled compounds: D-[2-14 C]-glucose, L(+)-[3-14 C]-lactate, and D(-)-3-hydroxy-[3-14C]-butyrate. These were chosen because they are the isomers preferred by the relevant enzymes in situ and the selected specific positions of the 14 C label have particular advantages for quantitative analyses (see Chapter 22 this volume).