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TCA Cycle Function and Reactions

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In the mammalian CNS there is a pyridoxal phosphate dependent glutamate decarboxylase that catalyzes the conversion of glutamate to gamma-amino butyric acid (GABA). This is an important inhibitory neurotransmitter.

GABA is subsequently degraded through transamination to succinic semialdehyde, with alpha-ketoglutarate as the NH3+ acceptor.

The succinic semialdehyde can then be oxidized to succinate, by succinate dehydrogenase.
a. Show how these reactions can operate as a shunt pathway that allows the TCA cycle to function without alpha-ketoglutarate dehydrogenase and succinate thiokinase.
b. Is the shunt more or less efficient than the TCA cycle in terms of energy recovery?

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Solution Summary

This solution includes a detailed discussion of (a) and (b) and a GABA shunt diagram. 420 words.

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Show how these reactions can operate as a shunt pathway that allows the TCA cycle to function without alpha-ketoglutarate dehydrogenase and succinate thiokinase."

In other words, normally, in the TCA, alpha-ketoglutarate is converted to succinyl-CoA, which is further converted to succinate. The two enzymes that do this are alpha-ketoglutarate dehydrogenase and succinate thiokinase. However, the GABA shunt bypasses these two enzymes and provides a way for the TCA to function without them. Therefore, we need to show that alpha-ketoglutarate can be converted to succinate through this GABA shunt.

Here's now it works:

The amino acid glutamate acts as the shuttle, being ...

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