Transport and metabolism of acetate in rat brain cortex in vitro

Abstract

1. [1-(14)C]Acetate undergoes metabolism when incubated aerobically at 37 degrees in the presence of rat brain-cortex slices, forming (14)CO(2) and (14)C-labelled amino acids (glutamate, glutamine, aspartate and relatively small quantities of gamma-aminobutyrate). In the absence of glucose the yield of (14)C-labelled aspartate exceeds that of (14)C-labelled glutamate and glutamine. The addition of glucose brings about a doubling of the rate of formation of (14)CO(2) and a greatly increased yield of (14)C-labelled glutamate or glutamine, whereas that of (14)C-labelled aspartate is diminished. 2. The addition of potassium chloride (100mm) to the incubation medium causes an increased rate of (14)CO(2) formation in the presence or absence of glucose and an increased rate of utilization of acetate. 3. The addition of 2,4-dinitrophenol (0.1mm) suppresses the rate of utilization of [1-(14)C]acetate. 4. The presence of ouabain (10mum) suppresses the rate of formation of (14)CO(2) from [1-(14)C]acetate and the rate of acetate utilization. Acetate conversion into carbon dioxide in the rat brain cortex is both Na(+)- and K(+)-dependent and controlled by operation of the active sodium-transport process. Only the Na(+)-stimulated rate is suppressed by ouabain. 5. Sodium fluoroacetate (1mm) decreases the rate of (14)CO(2) evolution from [1-(14)C]acetate in the presence of rat brain cortex without affecting the respiratory rate. The results are consistent with the conclusion that fluoroacetate competes with, or blocks, a transport carrier for acetate, so that in its presence only the passive diffusion rate of acetate takes place. 6. The presence of sodium propionate or sodium butyrate suppresses the utilization of [1-(14)C]acetate in rat brain cortex and leads to a concentration ratio (tissue/medium) of [1-(14)C]-acetate greater than unity. 7. The presence of NH(4) (+) diminishes acetate utilization, this being attributed to a diminished ATP concentration. Glycine is also inhibitory. It is concluded that acetate transport into the brain is carrier-mediated and dependent on the operation of the sodium pump.

Biochemistry of Selected Amino Acids

“…In addition, carbon from labeled fatty acids and labeled pyruvate was incorporated into amino acids in sheep brain (123) and rat brain, (125) respectively. Investigations with brain slices or homogenates have provided similar data, (62,(126)(127)(128)(129)(130) as also have experiments with excised ganglia. (131) The experimental data thus obtained has led most investigators to suggest that glucose in brain is rapidly metabolized to pyruvate and IX-ketoglutarate.…”

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

“…Greater uptake and metabolism of (Gonda and Quastel, 1966;Berl et al, 1970). Depolarization also accelerates labeling of glutamine (and glutamate) by [1- 13 C]glucose, which is not detectable under resting conditions, suggesting an increased contribution of glucose to glial metabolism (Badar-Goffer et al, 1992).…”

Astrocyte activation in vivo during graded photic stimulation

“…Several studies support the hypothesis that [ 14 C]acetate utilization is modulated by shifts in cation levels in adult brain tissue: (i) K + -induced spreading cortical depression increases acetate utilization by 20-40% rat brain in vivo (Dienel et al 2001a); (ii) inclusion of 5 mmol/L glucose, 100 mmol/L KCl, or 100 mmol/L KCl plus 100 mmol/L NaCl in the medium for rat brain slices increases 14 CO 2 formation from [ 14 C]acetate, whereas ouabain and fluoroacetate suppress acetate oxidation (Gonda and Quastel 1966); and (iii) ouabain, 40-100 mmol/L Li + , low [Ca 2+ ] in the medium, or low O 2 pressure reduce [ 14 C]acetate uptake and incorporation into amino acids in guinea pig brain slices (Berl et al 1970a,b;Berl and Clarke 1972). Thus, flux in astrocytic oxidative pathway rises during stimulatory conditions and changes in cation levels modulate oxidative metabolism of [ 14 C]acetate in situ and in vivo.…”