STRUCTURAL CHARACTERIZATION OF VARIANT FORMS OF ARYLSULFATASE A THAT ASSOCIATE WITH ALCOHOLISM

Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type IIIa and normal type IVa have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic popu lation that we have analyzed is enriched in variant type IIIa compared with nonalcoholic psychiatric and normal controls. Individuals with t he IIIa enzyme possess greatly reduced levels of ASA activity. To unde rstand further the structural basis for the differences and their pote ntial biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electroph oretic patterns of fibroblast ASA from the IIIa and IVa individuals di ffer in degree of phosphorylation. Furthermore, fibroblast ASA from II Ia individuals lacks an N-linked glycan found in ASA from IVa individu als. In addition, differences in peptide and/or posttranslational modi fication unrelated to the N-linked carbohydrate or phosphorylation exi st between the fibroblast ASA from IIIa and IVa individuals. The findi ng that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for th e use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.