Premium
Stabilising normal and mis‐sense variant α‐glucosidase
Author(s) -
Kakavanos Revecca,
Hopwood John J.,
Lang Debbie,
Meikle Peter J.,
Brooks Doug A.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.096
Subject(s) - enzyme , alpha glucosidase , alpha (finance) , chemistry , biochemistry , glycogen , glycogen storage disease type ii , enzyme assay , fibroblast activation protein, alpha , in vitro , glycogen storage disease , endocrinology , medicine , biology , enzyme replacement therapy , disease , construct validity , nursing , cancer , patient satisfaction
α‐Glucosidase (EC 3.2.1.3) is a lysosomal enzyme that hydrolyses α‐1,4‐ and α‐1,6‐linkages of glycogen to produce free glucose. A deficiency in α‐glucosidase activity results in glycogen storage disorder type II (GSD II), also called Pompe disease. Here, d ‐glucose was shown to be a competitive inhibitor of α‐glucosidase and when added to culture medium at 6.0 g/L increased the production of this protein by CHO‐K1 expression cells and stabilised the enzyme activity. d ‐Glucose also prevented α‐glucosidase aggregation/precipitation and increased protein yield in a modified purification scheme. In fibroblast cells, from adult‐onset GSD II patients, d ‐glucose increased the residual level of α‐glucosidase activity, suggesting that a structural analogue of d ‐glucose may be used for enzyme enhancement therapy.