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Structural Characterization of Variant Forms of Arylsulfatase A that Associate with Alcoholism
Author(s) -
Park David S.,
Manowitz Paul,
Stein Stanley,
Poretz Ronald D.
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01635.x
Subject(s) - fibroblast , phosphorylation , platelet , population , biochemistry , microbiology and biotechnology , biology , chemistry , medicine , in vitro , immunology , environmental health
Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type III a and normal type IV a , have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type III a compared with nonalcoholic psychiatric and normal controls. Individuals with the III a enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the III a and IV a individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from III a individuals lacks an N ‐linked glycan found in ASA from IV a individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N ‐linked carbohydrate or phosphorylation exist between the fibroblast ASA from III a and IV a individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.