GABA + a-Ketoglutarate *------> glutamate + succinic semialdehyde ssadh

Succinic semialhehyde + NAD+ -ยป succinate + NADH + h +

Figure 3.13. GABA-transaminase catalyzes the breakdown of GABA. GABA-T, GABA trans aminase; SSADH, succinic semialdehyde dehydrogenase.

1993). GABA-transaminase, a pyridoxal phosphate-dependent enzyme with high substrate specificity for GABA and a-ketoglutarate, carries out the initial step involving transamination of a-ketoglutarate to glutamate (Fig. 3.13). In the next step, succinic acid semialdehyde dehydrogenase oxidizes succinic semialdehyde to succinate. Succinate then enters the TCA cycle through succinate dehydrogenase. Succinic semialdehyde is not found in the nervous tissue because it is rapidly oxidized, and the activity of succinic acid semialdehyde dehydrogenase (SSADH) is normally higher than that of GABA-T making transamination the rate limiting step (Kugler, 1993). SSADH also has a low Km and hence the transamination reaction becomes essentially irreversible in vivo.

3.3.2. GABA Shunt

The GABA shunt is a closed pathway whose purpose is to produce and conserve the supply of GABA (Fig. 3.14). The first step in the process is the

O NH2 O ho-c-chch2ch2c-oh Glutamate GAD

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