Hi, I have a question about how to relate the glutamate dehydrogenase enzyme with other mitochondrial enzymes, which are directly involved in the TCA cycle. I need to know, whether changes in the GDH activity will affect the end product of TCA cycle?
Dear Saranya,
Changes in glutamate dehydrogenase activity has an effect on the end products of the TCA cycle.
The citric acid cycle is regulated by three simple mechanisms:
1. Substrate availability
2. Product inhibition
3. Competitive feedback inhibition.
The allosteric effectors that control the flux of metabolites through the citric acid cycle are shown on the next pate. The principle signals are acetyl-CoA, succinyl-CoA, ATP,ADP, AMP, NAD+ and NADH. All of the regulatory enzymes of the citric acid cycle including pyruvate dehyrogenase are allosterically inhibited by NADH. The combination of the electron transport chain and oxidative phosphorylation
produce ATP form NADH, consequently ATP is an allosteric inhibitor of pyruvate dehydrogenase and isocitrate dehydrogenase. The TCA cycle is turned on however by high ratios of either ADP/ATP or NAD+/NADH which indicate that the cell has run low of NADH or ATP.
A figure illustrating the connection between GDH and TCA is depicted in page 3 of the attached file (TCA 1).
For more on this topic , please see the publication contained in the following link:
http://themedicalbiochemistrypage.org/tca-cycle.php
Hoping this will be helpful,
Rafik
One of the products of the reaction of glutamate dehydrogenase is 2-oxoglutarate, which feeds into the citric acid cycle for ATP production.
Glutamate dehydrogenase is directly linked to the TCA cycle and competes with the TCA cycle enzyme 2-oxoglutarate dehydrogenase for the same precursor: 2-oxoglutarate, an intermediate of the cycle.
A change in activity of GDH will therefore likely directly impact the flux through the cycle. This is for example important, when engineering bacteria for enhanced glutamate production, where the carbon flux is rediected from the TCA cycle towards glutamate.
Best
Christoph
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