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Transferase and epimerase galactosemias are metabolically distinct disorders
Author(s) -
Ross Kerry Lynn,
FridovichKeil Judith L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a97
Subject(s) - galactosemia , galactokinase , galactose , phenotype , medicine , endocrinology , enzyme , biology , transferase , biochemistry , gene , escherichia coli
α‐D‐Galactose is metabolized by galactokinase (GALK), galactose‐1‐P uridylyltransferase (GALT), and UDP galactose‐4‐epimerase (GALE). Impairment of this pathway in humans results in the disorder galactosemia, with either GALT or GALE deficiencies resulting in more severe phenotypes. Currently, GALT deficiency is the best understood, although the basis of pathophysiology remains unclear. Galactose restriction is the only known treatment for galactosemia, and despite early intervention, many patients experience serious life‐long complications. Here we have addressed whether GALT and GALE deficiency galactosemias are similar or distinct disorders in terms of metabolic abnormality. Cultured human fibroblasts, derived from control, GALT‐impaired, or GALE‐impaired patients were exposed to galactose and their metabolic response determined. Within 24h, galactose utilization was comparable among the three cell types. However, unlike the control, both the GALT and GALE deficient cells accumulated abnormally high levels of gal1P. The GALE impaired cells also accumulated UDPgal, while the GALT deficient cells did not. Our results demonstrate distinct changes in metabolites in these cells in response to galactose exposure, and set the stage for future experiments designed to test the relationship between specific enzyme activities, levels of specific metabolites, and galactose‐induced functional impairment. (NIH Supported)