Utilization in vivo of glucose and volatile fatty acids by sheep brain for the synthesis of acidic amino acids

Abstract

1. Free glutamic acid, aspartic acid, glutamic acid from glutamine and, in some instances, the glutamic acid from glutathione and the aspartic acid from N-acetyl-aspartic acid were isolated from the brains of sheep and assayed for radioactivity after intravenous injection of [2-(14)C]glucose, [1-(14)C]acetate, [1-(14)C]butyrate or [2-(14)C]propionate. These brain components were also isolated and analysed from rats that had been given [2-(14)C]propionate. The results indicate that, as in rat brain, glucose is by far the best precursor of the free amino acids of sheep brain. 2. Degradation of the glutamate of brain yielded labelling patterns consistent with the proposal that the major route of pyruvate metabolism in brain is via acetyl-CoA, and that the short-chain fatty acids enter the brain without prior metabolism by other tissue and are metabolized in brain via the tricarboxylic acid cycle. 3. When labelled glucose was used as a precursor, glutamate always had a higher specific activity than glutamine; when labelled fatty acids were used, the reverse was true. These findings add support and complexity to the concept of the metabolic ;compartmentation' of the free amino acids of brain. 4. The results from experiments with labelled propionate strongly suggest that brain metabolizes propionate via succinate and that this metabolic route may be a limited but important source of dicarboxylic acids in the brain.

Cerebral metabolism of [1,2‐13C2]glucose and [U‐13C4]3‐hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy

“…Using [l ,2-13C2]gIucose as substrate, the pyruvate carboxylation reaction (via [2,3-'3C,]pyruvate) produces [2, and, in the first turn of the TCA cycle, also [2,3-13C2]glutamate and glutamine. In contrast, the incorporation of label via the pyruvate dehydrogenase reaction produces fairly small amounts of these isotopomers and only after heavy cycling of the label in the TCA cycle.…”

Biochemistry of Selected Amino Acids

“…Nevertheless, alanine, glutamate, glutamine, aspartate, and y-aminobutyrate have been isolated with quite high specific activities and proline, arginine, serine, glycine, glutathione, and N-acetyl aspartic acid with somewhat lower specific activities. 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.…”

Simultaneous detection of cerebral metabolism of different substrates by in vivo 13C isotopomer MRS

“…However, the brain does not use glucose as its only energy source (e.g., glycogen is found to be an energy reserve of significance; Cruz and Dienel, 2002; Choi et al, 1999), particularly during ontogenic development, fasting and diabetes. Under a variety of pathological conditions, ketone bodies including β-hydroxybutyrate (BHB) and acetoacetate (AcAc), lactate and free fatty acids can be used as alternative fuels for energy production (O'Neal R et al, 1966; Lundquist et al, 1973; Hawkins, 1986; Edmond, 1992; Shen et al, 1998; Guzman and Blazquez, 2001; Lebon et al, 2002; Al-Mamun et al, 2009). Sometimes, even alcohol can act as an indirect or abnormal cerebral oxidative energy substrate in subjects of chronic alcoholism (Zakhari, 2006) due to its direct byproduct acetate being metabolized by glial cells in the brain.…”

“…In recent decades, there has been a long-standing interest in compartmentalization, energy metabolism and neurotransmission in the brain. However, partly due to technical difficulties, the majority studies in this field have focused on detecting the cerebral metabolism of a single substrate in the brain (e.g., Cremer, 1964; O'Neal R et al, 1966; Hassel et al, 1995; Sibson et al, 1997; Waniewski and Martin, 1998), and few studies have investigated the simultaneous metabolism of multiple energy substrates.…”