Metabolism of brain and Nerve ( pages 522-3) Year 1969
- When a nerve is stimualted to conduct an impulse, a small but measured amount of heat is produced. The heat is produced in two stages, as it is in working muscle. This suggests that rapidly released initial heat represents the energy involved in transmission of the impulse, and that the delayed or recovery heat ( which may continue for 30 to 45 minutes) is released to restoration of the energy mechanisms. Similarly, the nerve may conduct impulses and develop heat under anaerobic conditions as, for example, in an atmosphere of nitrogen; but recovery depends on the admission of oxygen, as indicated by extra consumption of readmitted oxygen.
- The respiratory quotient of metabolizing nerve is very close to 1, which suggests that the nerve is utilizing carbohydrate almost exclusively. Recent studies with rat brain mitochondria (1963) indicate that, contrary to earlier assumptions, brain mitochondria are not capable of oxidizing glucose. Glycolytic enzymes are apparently contained only in soluble cytoplasmic material of some cellular fragments present as contaminants of the original mitochondrial preparations, which thus appear to possess glycolytic acivity. Mitochondria do, however appear to possess significant quantities of the hexokinase activity identified in preparations from rat brain.
- The metabolism of carbohydrate in nerve tissue seems to be similar to that of muscle, since lactic and pyruvic acids appear under anaerobic conditions. These end-products disappear very slowly; oxygen does not accelerate the process.
- The synthesis of glycogen by brain tissue has been shown to take place by way of uridine diphosphate glucose (UDPG) as was described for liver and muscle. the glycogen stores of brain and nerve are very small; hence a minute-to-minute supply of blood glucose is particularly important for nervous system. this may be the major reason for the prominence of nervous symptoms in hypoglycemia.
- Glutamic acid (GLU) seems to be the only aminoacid metabolized by brain tissue. However, this amino acid is of considerable importance in brain metabolism. It serves as a precursor of gamma-aminobutyric acid (GABA) and is a major acceptor of ammonia (NH3) produced either in metabolism of the brain or delivered to the brain when arterial blood ammonia is elevated. In this latter reaction, glutamic acid (GLU) accepts 1 mol of ammonia and is thus converted to glutamine (GLN).
- Although it has been shown that the brain can form ure a(1959), the formation of urea does not play a significant role in removal ammonia in the brain. This is accomplished almost entirely by reactions involving the formation of glutamic acid (GLU) by amidation of ketoglutaric acid (KG) as well as by the formation of glutamine (GLN).
- When the levels of ammonia in the brain are elevated, usually as a result of increased ammonia in the blood, the supply of glutamic acid (GLU) available from the the blood may be insufficient to form the additional amounts of glutamine (GLN) required to detoxify the ammonia in the brain. Under these circumstances glutamic acid is synthesized in the brain by amination of the ketoglutaric acid (KG) produced in the citric acid cycle within the brain itself. However, continuous utilization of ketoglutaric acid for this purpose would rapidly deplete the citric acid cycle of its intermediates unless a method of replenishing the cycle were available. Depletion is accomplished by CO2-fixation, involving pyruvate to form oxaloacetic acid (OA), which enters to the citric acid cycle and proceeds to the formation of ketoglutarate (KG). The reaction in brain is precisely analogous to that which occurs in the liver.
- Fixation of CO2 in isolated retinal tissue was demonstrated 1951. Studies of CO2-fixation in brain have been described 1962. These authors have found that CO2 fixation into aminoacids occurs to a significant degree in the cerebral cortex. The highest specific activity among metabolites in the brain was found in aspartate (ASP), which would be expected if the initial reaction involved formation of malate and then oxaloacetate, this latter compound forming aspartate by transamination. However, after infusion of ammonia, it was apparent that oxaloacetate (OA) was now being used for the synthesis of ketoglutarate (KG), glutamate (GLU) nad glutamine (GLN) at faster rate than it was being converted to aspartate (ASP). This suggests that ammonia causes channelling of oxaloacetate to the formation of glutamine (GLU).
- The formation of gamma-aminobutyrate (GABA) in central nervous system tissue from glutamtae GLU) has been discussed on page 350. the significance of GABA as an important regulatory factor in neuronal activity has also been mentioned.
- The synthesis of long-chain fatty acids (LCFA) by entzyme preparations from rat brain tissue has been demosntrated by brady( 1960). The pathway of synthesis was that of the extramitochondrial system. in which malonyl coenzyme A is a required intermediate.
- From the examples cited above and the results of other recent( 1969) investigations of brain metabolism, it is becoming apparent that cerebral tissue possesses all enzymatic activity necessary to support major metabolic pathways which are found in other organs of the bodyThis has been referred to as the "autonomy of cerebral metabolism".
- The ability of the brain to fix CO2 introduces interestin speculations with respect to the influence of CO2 on the operations of the citric acid cycle in the brain. because the metabolism of glucose provides virtually the sole source of energy for brain emtabolism, if CO2 tension did exert a controlling influence on the citric acid cycle an additional ecplanation for the effects of CO2 on the brain might be forthcoming.
GLU reseptorit NMDA ja AMPA http://www.sumanasinc.com/webcontent/animations/content/receptors.html
ASP : Aspartate (the conjugate base of aspartic acid) stimulates NMDA receptors, though not as strongly as the amino acid neurotransmitter L-glutamate does.