BackgroundInformation | GAD65isagroupIIdecarboxylaseenzymethatcatalyzesthebiosynthesisofGABAfromglutamatewiththeaidofthecofactor,pyridoxal5"-phosphate.GAD65localizesatpresynapticGABAergicterminalsandisreportedtosupplylocalvesicularpoolsofGABAfacilitatingtransientinhibitioryneurotransmission,althoughGAD65mayalsoplayaroleinmoresustainedtonicinhibitorysignals.Itispresentasadimerofalphaandbetasubunitsandisregulatedbyalternativesplicing,whichmayproducetheGAD67isoform.GAD65alsoundergoespost-translationalmodificationssuchaspalmitoylationofN-terminalcysteineresiduesandphosphorylationofmultiplealpha-subunitserineresiduesthatenablemembrane-anchoringandothervesicularactivities.GAD65hasbeenimplicatedinneurologicalconditionsresultingfromfailureofinhibitoryneurotransmissionsuchasHuntington"sdiseaseandepilepsy.InadditiontoitsCNSpresence,GAD65alsoproducesGABAinpancreaticbetacellsanddysfunctioninthisareamaycontributetothepathogenesisofinsulin-dependentdiabetesmellitus. |