AN INTEGRAL MEMBRANE-PROTEIN FORM OF BRAIN L-GLUTAMATE DECARBOXYLASE - PURIFICATION, CHARACTERIZATION AND ITS RELATIONSHIP TO INSULIN-DEPENDENT DIABETES-MELLITUS

A new and novel form of L-glutamate decarboxylase (GAD; EC 4.1.1.15) w as purified from whole porcine brain to apparent homogeneity by a comb ination of column chromatographies on DE-52, ultragel AcA 34, hydroxyl apatite and Sephadex G-200, and native gel electrophoresis. The purifi ed GAD was established as an integral membrane protein based on hydrop hobic interaction chromatography and membrane extraction studies. This membrane GAD (MGAD) has a native molecular weight of 120+/-5 kDa and is a homodimer of 60+/-2 kDa. Immunoprecipitation and immunoblotting t ests using the sera from insulin-dependent diabetes mellitus (IDDM) pa tients revealed the presence of antibodies against this newly identifi ed MGAD in IDDM. The role of MGAD in the pathogenesis of IDDM and rela ted autoimmune disorders is also discussed.