METABOLISM OF GLUCOSE AND FREE AMINO ACIDS IN BRAIN, STUDIED WITH ¹⁴C‐LABELLED GLUCOSE AND BUTYRATE IN RATS INTOXICATED WITH CARBON DISULPHIDE

Abstract

Abstract— The effect of 15 h continuous exposure to CS2 on the metaboliam of glucose and free amino acids in the brain of rats was studied. CS2 caused a moderate hypoglycaemia. There were also changes in the amounts of some amino acids in the brain. Glutamate and γ‐aminobutyrate were lower whereas glutamine was markedly increased. Comparative studies in vivo of the metabolism of [2‐14C]glucose and [1‐14C]butyrate indicated that CS2 did not affect glycolysis or the incorporation of 14C from glucose into amino acids except into γ‐aminobutyrate which was reduced. Contrary to the findings with [14C]glucose, CS2 provoked distinct changes in the labelling of amino acids when [14C]butyrate was the precursor. The most notable change was a markedly increased incorporation of 14C into glutamine. Based on the two‐compartment model of brain glutamate the experimental findings indicated that CS2 affected metabolism associated with the ‘small’ pool of glutamate but had a minimal effect on metabolism associated with the ‘large’ glutamate pool. The possibility is suggested that the changes observed involved an increased rate of ammonia removal. The low incorporation of 14C into γ‐aminobutyrate from either precursor is consistent with other evidence showing that CS2 interferes with pyridoxal phosphate‐dependent enzymes.

Local uptake of 14C‐labeled acetate and butyrate in rat brain in vivo during spreading cortical depression

“…For example, after 2 hr of exposure to triethyltin, the uptake of [1- 14 C]acetate into rat brain at 3 and 10 min after an intravenous injection was the same as control, and the glutamine RSA ranged from 2.1-3.7 (Cremer, 1970). Exposure of rats to carbon disulfide for 15 hr increased [1- 14 C]butyrate incorporation into glutamine compared to controls, and the glutamine RSA determined 1-10 min after the intravenous injection of acetate or butyrate was Ͼ2.9 in the treated rats (Tarkowski and Cremer, 1972). In portacaval-shunted rats, which have chronic hyperammonemia, striking changes in astrocyte morphology (e.g., swelling and reactive changes), and *Values are mean Ϯ SD (n ϭ 4).…”

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

“…From our kinetic data the morphological structures metabolizing the pyruvate plus lactate formed from the glucose entering the brain appear to be the same as those metabolizing the acetoacetate and 3-hydroxybutyrate entering from the blood. It is notable that when 14C-labelled acetoacetyl-CoA is formed within the brain during the oxidation of leucine (Patel & Balazs, 1970) or butyrate (Tarkowski & Cremer, 1972) the specific-radioactivity-time curves for glutamate and glutamine are completely different from those observed when acetoacetyl-CoA is formed from blood-borne ketone bodies.…”

Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat.

“…In each case a significantly lower plasma FFA concentration was observed in CS2-treated rats despite a small but significant hypoglycaemia (Table 2). Tarkowski and Cremer (1972) also report hypoglycaemia after 15 hours' exposure. Glycerol concentrations in plasma were measured as an indication of the rate of lipolysis in adipose tissue, but there were no significant differences in this parameter ( Table 2).…”