Glutamate metabolism and function of the brain.

microgram molecules/g microgram molecules/ml. "middle" 10.60.05N-acetyl tianmen winterline5.7< td align"middle" >- middle" >glutamine4.3< td align">"middle" γ <-aminotinic acid . 2.3--day door holline < "middle" > "middle" >0.01 tryptophan> 0.050.05

tt1" > as visible from Table 14-3, the free amino acid in the brain with the highest glutamate (Glu) content, which is more than 200 times higher than its concentration in plasma. The sum of glutamate, glutamine (Gln) and γ amino butyric acid (GABA) accounts for about half of the total amount of free amino acids in the brain. Therefore, glutamate occupies an important position in the amino acid metabolism of the brain.

However, glutamate is difficult to pass through the blood-brain barrier, glutamate in the brain comes from its own synthesis,isotope tracer experiments show that the raw material for glutamate synthesis in the brain is glucose, it comes from blood sugar. Glucose enters brain cells and then changes to α-ketone diacid (α-KG), which can be catalyzed into glutamate>dehydrogenase Glutamate can also be produced by trans-amino action, the longer approach is generally considered more practical, because glutamate dehydrogenase (GDH) catalytic reaction K mNH4 plus 8mM, much higher than the concentration of ammonia in cells. Glutamate binds to ammonia under the role of glutamine synthase to become glutamine, which is an energy-consuming reaction (consuming ATP), the brain glutamine synthase is highly active, its K mNH4 plus only 0.39mM. The resulting glutamine, unlike glutamate, can enter the blood through the blood-brain barrier, so that the braintissue from the blood intake of glucose, through metabolism, but also the blood glutamine, clear the brain ammonia, so as not to prevent the accumulation of ammonia harm the function of the brain.

Figure 14-1 Glutamate metabolism in the brain and the elimination of ammonia

brain Another feature of glutamate metabolism is the production of γ-amino butyric acid (a.k.a. γ-acetic gba), and the enzyme that catalyses this reaction is glutamate dehydrase (GAD), which requires acetaldehyde phosphate as a coenzyme. GABA is an inhibitory neurotransmitter found only in the central nervous system. GabA in the brain is mainly stored in gray mass, especially in the synth, black, cer cerebral toothy nuclei and so on.

< gabA has a universal inhibitory effect on > neurons by using the p class .tt1. In 1963, it was suggested that GABA could act on pre-synapse nerve endings, reducing the release of excitable deliveries, which can lead to inhibition. This effect is called presynaptic inhibition. GABA's role in the spinal cord is dominated by pre-synapse inhibition. In the brain GABA mainly causes post-synapse inhibition (postsynaptic inhibition). The release of GABA from the cortical layer during sleep has increased, so it is thought that GABA may be related to the physiological function of sleep and wakefulness.

Figure 14-2a Brain TCA circulation and GABA metabolic bypass

Figure 14-2b GAD and GABA-T role

in nerves The mitochondrials of metacytospherics and synapses (synapse) contain a large amount of γ-aminobunic acidtransaminase (GABA-T), which catalyses the transamination between GABA and α ketone diacids to produce succinic acid semialdehyde and glutamate. This can be seen as a way for GABA to inactivation. GABA-T is also the need for phosphate acetaldehyde as coenzyme, but compared with GD, it and phosphate acetaldehyde affinity is large, so when the bodyvitaminB6 deficiency, the main impact on the activity of GED. For example, when using isoniazid to treat tuberculosis, because isoniazid can be combined with vitamin B6 (isoniazone), accelerate the excretion of vitamin B6 from the urine, causing the concentration of vitamin B6 in brain tissue decreased, GAD activity also decreased, the result of GABA synthesis is blocked, easy to make the center overexcitement and convulsions and other symptoms. Therefore, vitamin B6 should be combined when using isoniazid for a long time. In addition, clinically for convulsions, pregnancy vomiting patients, also often use vitamin B6, the rationale is also to improve the activity of GABA in brain tissue, so that GABA production increased, central inhibition is relatively strengthened.

Figure 14-3 GAD and GABA-T the most appropriate role pH

GABA transaminated product amber acid semialdehyde can be dehydrogenated to produce amber acid, the latter entered the triacetonic acid cycle is oxidized and utilized. Therefore, there is a GABA metabolic bypass (GABa shunt) that is connected to the tricarbonate cycle in brain tissue.

< the synergy between >p class>glutinine dehydrase and γ-aminobutaminase is important to maintain a certain concentration of GABA in the brain. The most appropriate pH for both enzymes is different, with GAD's suitable pH at 6.5 and GABA-T at pH8.2. (Figure 14-3) It can be seen that a slight change in pH in brain cells can significantly change the activity of the two enzymes. When acidosis, GABA-T activity in the brain is enhanced and GABA-T activity decreases, which can cause GABA levels in the brain to rise, showing central inhibition;

still need to point out that glutamate has an excitation effect on the nerve center, while its dehydration product GABA has an inhibitory effect, so glutamate metabolism is related to the central excitement and inhibition regulation. In addition, the oxidation metabolism of the brain is also linked to the function of excitation inhibition by GABA metabolic bypass.

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