Biomaterial Database

Influence of L-fucose attached alpha 1-->6 to the asparagine-linked N-acetylglucosamine on the hydrolysis of the N-glycosidic linkage by human glycosylasparaginase. 1997

T Noronkoski, and I Mononen

Department of Clinical Chemistry, Kuopio University Hospital, Finland.

The sequence of hydrolytic reactions in the catabolism of the N-glycosidic oligosaccharide-to-protein region containing 6-linked fucose on the asparagine-linked N-acetylglucosamine may vary from species to species. When alpha-L-fucopyranosyl-(1-->6)-2-acetamido-1-N-(beta-L-aspartyl)-2-deoxy- beta -D-glucopyranosylamine (Fuc-GlcNAc-Asn) was incubated with recombinant human glycosylasparaginase, no hydrolysis of the N-glycosidic bond was detected. After removal of the alpha 1-->6-linked fucose from the compound by alpha-fucosidase, the residual GlcNAc-Asn was rapidly hydrolyzed by glycosylasparaginase. Enzymologically this demonstrates for the first time that the catabolism of Fuc-GlcNAc-Asn in humans occurs via consecutive action of alpha-fucosidase and glycosylasparaginase. The hydrolysis rate of GlcNAc-Asn by glycosylasparaginase remained unaffected in the presence of Fuc-GlcNAc-Asn or several different monosaccharides including fucose. This indicates that any fucose attached alpha 1-->6 to the asparagine-linked N-acetylglucosamine residue prevents the access of the L-asparagine residue of Fuc-GlcNAc-Asn into the deep, funnel-shaped active site of human glycosylasparaginase. These findings explain the accumulation of fucosylated and normal catabolism of nonfucosylated glycoasparagines in fucosidosis.

UI	MeSH Term	Description	Entries
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005643	Fucose	A six-member ring deoxysugar with the chemical formula C6H12O5. It lacks a hydroxyl group on the carbon at position 6 of the molecule.	Deoxygalactose,alpha-Fucose,alpha Fucose
D005644	alpha-L-Fucosidase	An enzyme that catalyzes the hydrolysis of an alpha L-fucoside to yield an alcohol and L-fucose. Deficiency of this enzyme can cause FUCOSIDOSIS. EC 3.2.1.51.	Fucosidase,alpha-Fucosidase,alpha Fucosidase,alpha L Fucosidase
D005645	Fucosidosis	An autosomal recessive lysosomal storage disease caused by a deficiency of ALPHA-L-FUCOSIDASE activity resulting in an accumulation of fucose containing SPHINGOLIPIDS; GLYCOPROTEINS, and mucopolysaccharides (GLYCOSAMINOGLYCANS) in lysosomes. The infantile form (type I) features psychomotor deterioration, MUSCLE SPASTICITY, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, SEIZURES, recurrent infections, and MACROGLOSSIA, with death occurring in the first decade of life. Juvenile fucosidosis (type II) is the more common variant and features a slowly progressive decline in neurologic function and angiokeratoma corporis diffusum. Type II survival may be through the fourth decade of life. (From Menkes, Textbook of Child Neurology, 5th ed, p87; Am J Med Genet 1991 Jan;38(1):111-31)	Fucosidase Deficiency Disease,Alpha-Fucosidase Deficiency,Deficiency Disease, alpha-Fucosidase,Deficiency Disease, alpha-L-Fucosidase,Fucosidase Deficiency,Fucosidosis Type 1,Fucosidosis Type I,Fucosidosis Type II,Fucosidosis, Infantile,Fucosidosis, Juvenile,alpha-Fucosidase Deficiency Disease,alpha-L-Fucosidase Deficiency,alpha-L-Fucosidase Deficiency Disease,Deficiency Disease, Fucosidase,Deficiency Disease, alpha Fucosidase,Deficiency Disease, alpha L Fucosidase,Deficiency Diseases, Fucosidase,Deficiency Diseases, alpha-Fucosidase,Deficiency Diseases, alpha-L-Fucosidase,Disease, Fucosidase Deficiency,Disease, alpha-Fucosidase Deficiency,Disease, alpha-L-Fucosidase Deficiency,Diseases, Fucosidase Deficiency,Diseases, alpha-Fucosidase Deficiency,Diseases, alpha-L-Fucosidase Deficiency,Fucosidase Deficiency Diseases,Fucosidosis Type 1s,Infantile Fucosidosis,Juvenile Fucosidosis,Type 1, Fucosidosis,Type 1s, Fucosidosis,alpha Fucosidase Deficiency Disease,alpha L Fucosidase Deficiency Disease,alpha-Fucosidase Deficiency Diseases,alpha-L-Fucosidase Deficiency Diseases
D006027	Glycosides	Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)	Glycoside
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000117	Acetylglucosamine	The N-acetyl derivative of glucosamine.	Acetyl Glucosamine,N-Acetyl Glucosamine,N-Acetyl-beta-D-Glucosamine,N-Acetylglucosamine,beta-N-Acetylglucosamine,2-Acetamido-2-Deoxy-D-Glucose,2-Acetamido-2-Deoxyglucose,N-Acetyl-D-Glucosamine,2 Acetamido 2 Deoxy D Glucose,2 Acetamido 2 Deoxyglucose,Glucosamine, Acetyl,Glucosamine, N-Acetyl,N Acetyl D Glucosamine,N Acetyl Glucosamine,N Acetyl beta D Glucosamine,N Acetylglucosamine,beta N Acetylglucosamine
D001227	Aspartylglucosylaminase	An enzyme that catalyzes the conversion of N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine and water to N-acetyl-beta-D-glucosaminylamine and L-aspartate. It acts only on asparagine-oligosaccharides containing one amino acid, i.e. the ASPARAGINE has free alpha-amino and alpha-carboxyl groups. (From Enzyme Nomenclature, 1992)	Aspartylglucosaminidase,Aspartylglucosylamine Deaspartylase,Aspartylglycosamine Amidohydrolase,Aspartylglucosamine Amidohydrolase,Glycosylasparaginase,Amidohydrolase, Aspartylglucosamine,Amidohydrolase, Aspartylglycosamine,Deaspartylase, Aspartylglucosylamine
D013045	Species Specificity	The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.	Species Specificities,Specificities, Species,Specificity, Species
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities