A mutation in a highly conserved region in brush-border sucrase-isomaltase and lysosomal alpha-glucosidase results in Golgi retention.

A point mutation in the cDNA of human intestinal sucrase-isomaltase has been recently identified in phenotype II of congenital sucrase-isomaltase deficiency. The mutation results in a substitution of glutamine by proline at position 1098 (Q1098P) in the sucrase subunit. Expression of this mutant sucrase-isomaltase cDNA in COS-1 cells results in an accumulation of sucrase-isomaltase in the ER, intermediate compartment and the cis-Golgi cisternae similar to the accumulation in phenotype II intestinal cells.

An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus.

Orally taken alpha-glucosidase inhibitors are used for the management of diabetes mellitus. These drugs can prevent the postprandial rise of the blood glucose level by inhibiting the enzymatic digestion of carbohydrates in the intestinal lumen. Non-absorbable inhibitors such as acarbose are expected to function exclusively in the intestine, but absorbable inhibitors such as miglitol may exert an inhibitory effect on non-intestinal alpha-glucosidases present in the various cell types of the body.

Biochemical genetics of glycogenosis type II in Brahman cattle.

Glycogenosis type II is an inherited lysosomal storage disorder caused by acid alpha-glucosidase deficiency. The disorder is inbred in Brahman cattle, and the incidence of carriers in Australian herds averages 15%. Affected animals are lethargic and die typically in the eighth or ninth month after birth.

Human lysosomal alpha-glucosidase: functional characterization of the glycosylation sites.

N-linked glycosylation is one of the important events in the post-translational modification of human lysosomal alpha-glucosidase. Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor. The primary structure of lysosomal alpha-glucosidase, as deduced from the cDNA sequence, indicates that there are seven potential glycosylation sites.

The conservative substitution Asp-645-->Glu in lysosomal alpha-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II.

Glycogen-storage disease type II (GSDII) is caused by the deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the analysis of the mutant alleles in an American black patient with an adult form of GSDII (GM1935). The lysosomal alpha-glucosidase precursor of this patient has abnormal molecular features: (i) the molecular mass is decreased, (ii) the phosphorylation is deficient and (iii) the proteolytic processing is impaired.