Brain metabolic pools

As opposed to the two other endogenous excitatory amino acid candidates, cystelc acid and cysteine sulphinlc acid (15), glutamate (16) and aspartate (13) are found in abundant quantities in the mammalian CNS. Metabolically, aspartate and glutamate are related and their metabolism is quite complex. Thus, there are undoubtedly several metabolic pools of glutamate and aspartate, in addition to any neurotransmitter pool, making it difficult to study the biochemical aspects of their neurotransmitter action. Nevertheless, it has been shown that both substances are accumulated into brain tissue by a high affinity process, and that both can be released from brain tissue by electrical field stimulation. This behavior is characteristic of neurotransmitters. 

Engelsen B, Fonnum F (1983) Effects of hypoglycemia on the transmitter pool and the metabolic pool of glutamate in rat brain. Neurosci Lett 42 317-322. 

Fig. 1. Brain metabolic pathways for fatty acids. Thick arrows indicate major pathways followed rapidly by a FA after its entry into brain from plasma, and the enzymes involved in the pathways. Thin arrows indicate alternative pathways that are followed to a lesser extent within the 5- to 20-min experimental period of the FA method, the major one of concern from the acyl-CoA pool involving 3-oxidation within mitochondria (see text).

Tn recent years there has been a great deal of interest in understanding the mechanisms involved in ammonia metabolism in brain. The reasons for this interest are twofold ammonia is thought to be a major toxin contributing to the symptoms of encephalopathy associated with liver disease (1,2) and of Reye s disease (3) and earlier experiments with N-labeled ammonia suggested the existence of at least two distinct metabolic pools in brain (4). 

Glutamate has a central role in brain metabolism, as well as being a transmitter and a precursor for GABA. It is therefore of interest to define and quantify the different glutamate pools. The size of these pools will differ from area to area and species to species (Fig. 3). 

Fig. 3. Glutdimate cycles in the brain. The scheme shows the roles of glutamate in the brain. In the neuron, glutamate may act as a transmitter, precursor for GABA, or in the metabolic pool. An example is shown of how the three pools can be selectively destroyed in neostriatum. Glutamate is formed from glucose through the citric acid (TCA) cycle, from glutamine or 2-oxoglutarate. The latter two are derived from the glial cells.

NADH, which enters the Krebs cycle. However, during cerebral ischaemia, metabolism becomes anaerobic, which results in a precipitous decrease in tissue pH to below 6.2 (Smith etal., 1986 Vonhanweh etal., 1986). Tissue acidosis can now promote iron-catalysed free-radical reactions via the decompartmentalization of protein-bound iron (Rehncrona etal., 1989). Superoxide anion radical also has the ability to increase the low molecular weight iron pool by releasing iron from ferritin reductively (Thomas etal., 1985). Low molecular weight iron species have been detected in the brain in response to cardiac arrest. The increase in iron coincided with an increase in malondialdehyde (MDA) and conjugated dienes during the recirculation period (Krause et al., 1985 Nayini et al., 1985). 

With increasing metabolism of fat through p oxidation, much of the mitochondrial CoA pool may become tied up as acyl- or acetyl-CoA. In such cases, the supply of free CoA can be diminished, and this may limit the rate of p oxidation. Upon prolonged fasting and heavy reliance on fat for energy, the liver induces the enzymes required for the formation of ketone bodies and brain induces enzymes required for their metabolism. 

Under physiologic conditions, the balance of membrane lipid metabolism, particularly that of arachidonoyl and docosahexaenoyl chains, favors a very small and tightly controlled cellular pool of free arachidonic acid (AA, 20 4n-3) and docosahexaenoic acid (DHA, 22 6n-3), but levels increase very rapidly upon cell activation, cerebral ischemia, seizures and other types of brain trauma [1, 2], Other free fatty acids (FFAs) in addition to AA, released during cell activation and the initial stages of focal and global cerebral ischemia, are stearic acid (18 0), palmitic acid (16 0) and oleic acid (18 1). 

L-Tyrosine metabolism and catecholamine biosynthesis occur laigely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andUpid metabolism. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bile acids and the detoxification process of aromatic drugs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabolism related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

The altered copper metabolism in the aged is not explained by our data since it did not assess copper concentrations in other body pools rich in copper, but the fact that it did increase with age in males while serum ceruloplasmin failed to do so suggests that the level of free ionic copper or copper bound to a small polypeptide molecule is higher in these subjects than the level normally found in serum. Few studies have been reported on tissue copper concentration and its relation to age except for Schroeders work (15), alluded to earlier. He found that copper levels in liver and aorta are significantly decreased after the age of 60, whereas copper concentrations in the brain, kidney, spleen, and heart remain imchanged. 

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