07 - 7. GABA

7. GABA

© SPMM Course 7. GABA

•Glutamic acid (glutamate) Source Source •glutamic acid decarboxylase (GAD) catalysis Rate limiting step Rate limiting step •glutamic acid decarboxylase (GAD) Synthetic enzymes Synthetic enzymes •GABA transaminase Breakdown enzymes Breakdown enzymes •Broken down to glutamate, and then eventually to succinic acid Breakdown product Breakdown product •reuptake into both presynaptic nerve terminals and surrounding glial cells; uptake system is bidirectional and both temperature- and ion-dependent process; (inhibited by tiagabine) Reuptake Reuptake •Mediates anxiety, seizure cessation, and actions of benzodiazepines, barbiturates, and alcohol. Function Function •GABAA and GABAB •GABAA – opens chloride channel; inhibitory – leads to hyperpolarization; made of five subunits and at least 14 subunit subtypes •GABAB receptor is G-protein-coupled; baclofen is selective agonist Receptors Receptors •Role in anxiety disorders and alcoholism; may have a role in many other disorders including epilepsy and Huntington’s. Disorders Disorders