Glutamate Krebs cycle

Glutamic acid is formed m most organisms from ammonia and a ketoglutaric acid a Ketoglutaric acid is one of the intermediates m the tricarboxylic acid cycle (also called the Krebs cycle) and arises via metabolic breakdown of food sources carbohy drates fats and proteins... 

These points have important functional implications. While neuronal glutamate may come from glucose via pyruvate, the Krebs cycle and transamination of alpha-oxoglutamate, it seems likely that most of the transmitter originates from the deamination of glutamine. After release, the high-affinity uptake sites (transporters)... 

Figure B2(i) The pathway for conversion of proline and alanine in the flight muscle of the tsetse fly the major ATP-generating pathway. Alanine aminotransferase is essential for the proline oxidation pathway in order for glutamate to enter the Krebs cycle as oxoglutarate and pyruvate to be converted to alanine, the end of the pathway. It is assumed that the pathway is the same for the Colorado beetle, but no studies have been reported.

Figure 9.4 Reactions of glutaminolysis the pathway for glutamine oxidation. Reaction 1 is catalysed by glutaminase, reaction 2 by glutamate aminotransferase, and reaction 8 by aspartate aminotransferase all other enzymes are those of the Krebs cycle (3-7). (See also Chapter 8).

It interferes with metabolic pathways of amino acids leading from glutamic acid to the citric acid (Krebs) cycle and urea. 

Krebs cycle is inhibited at the points where a-ketoglutarate dehydrogenase and succinate dehydrogenase operate. This causes an increase in organic acids and an accumulation of glutamate. 

Pyruvate, from glycolysis of glucose, is carboxylated to oxaloacetate or oxidized to acetyl-CoA. These metabolites enter the Krebs cycle, are metabolized to a-ketoglutarate and oxaloacetate, then transaminated to aspartate or glutamate. Asn, Gin, and Pro are synthesized from Asp or Glu. The cycle replenishes intermediates via the anaplerotic reactions (e.g., car-boxylation of pyruvate to form oxaloacetate). 

Fig. 7. Glutamate and glutamine synthesis in relation to the Krebs cycle.

Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate is formed by the Krebs cycle and is found free and stored in vesicles in synaptic terminals. Its release is calcium dependent, and an uptake system exists in presynaptic terminals and in glia to terminate its action after release. It is possible that glia metabolize glutamate to glutamine and return it to the neuron for reuse. An excessive release of glutamate can be lethal to cells in the immediate vicinity. 

Since C->2 and C-3 of glutamate are labeled and C-4 is not, all of the [3- C]-pyruvate derived from [3- C]-alanine enters the Krebs cycle as oxaloacetate These results indicate that acetylCoA, which is required for Krebs cycle activity, is derived from an unlabeled pool, probably from the mobilization and oxidation of endogenous lipids in the liver ... 

It connects with the Krebs cycle of the Main Powerhouse via the Urea Rest Room, as aspartate and glutamate, which are spun off the Krebs Cycle are important participants in die Urea Cycle. Also, 3-aminobutyrate, a product of thymine degradation, may connect to succinyl CoA. 

Glutamate (Glu) is the most abundant amino acid in the CNS. About 30% of the total Glu acts as the major excitatory neurotransmitter in the brain. Glu is synthesized in the nerve terminals from tw o sources from glucose via the Krebs cycle and from glutamine by the enzyme glutaminase. The production of the neurotransmitter glu is regulated via the enzyme glutaminase. Glu is stored in vesicles and released by a Ca " dependent mechanism. 

The histidine catabolic pathway is discussed under Folate in Chapter 9. The material reveals that histidine is catabolized to produce glutamate. Glutamate in turn, can be converted to a-ketoglutarate and completely oxidized to CO in the Krebs cycle. In the study depicted in Figure 8,26, the dietary histidine was spiked with I Cjhistidine, The term "spiked" means that only a very small proportion of the histidine contained carbon-14. The metabolic behavior of the radioactive histidine, which can be followed, mirrors the metabolic fate of nonradioactive histidine in the diet. All of the CQz exhaled by the rats can be easily collected, The " COj present in the rat s breath can be measured by use of a liquid scintillation counter. The amount of CO2 produced directly mirrors the proportion of histidine, absorbed from the diet that was degraded the rat s body. 

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