ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The properties of N-acetylgalactosamine-6-sulfate (GalNAc-6-S) sulfatase (EC 3.1.6.?) in normal fibroblasts were compared with those in fibroblasts from patients with different phenotypic expressions of Morquio disease type A (mucopoly-saccharidosis IV A). The two patients exhibiting a mild variant of the disorder could be distinguished from the classical form of the disease by the absence of gross dysmorphic features of the face, absence of neurological defects, less reduced body height, and by less pronounced radiological abnormalities.Using a disulfated trisaccharide prepared from chondroitin-6-sulfate as substrate of GalNAc-6-s sulfatase, the enzyme from normal fibroblasts exhibited a sharp pH optimum at pH 4.0 when assayed in 0.02 M sodium acetate buffer. At this pH the normal range of activity was 13–67 nmole/hour and mg cell protein. The fibroblast enzyme activity of severely affected individuals was about 1 nmole/hour and mg protein with the highest residual activity at pH 3.0 (0.02 M sodium formate buffer). The enzyme of one of the mild variants was maximally active at pH 4.0 with a value of approximately 0.8 nmole/hour and mg protein, whereas that of the other one gave a pH activity curve which was a composite of the latter two profiles. At the respective pH optima the residual activities did not differ significantly. The mutant enzymes had with 15 μmole/1 the same Michaelis constant as the normal GalNAc-6-S sulfatase but they were all more thermolabile than their normal counterpart. Complementation after fusion of fibroblasts from different types of patients did not occur.SpeculationThe phenotypic expression of Morquio disease type A might depend on the residual activity of GalNAc-6-S sulfatase at the pH which is physiologically reached in lysosomes. This pH is most likely above the pH optimum of the sulfatase. In spite of similar residual activities among the patients that mutation which causes a shift of the pH profile of the enzyme to the more acidic side would lead to a more impaired degradation of storage material. This might cause more severe clinical symptoms than a mutation which does not affect the pH optimum of the enzyme.Additionally, our results might provide a method to prognosticate the course of the disease.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID