Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-1-21
pubmed:abstractText
Human lysosomal beta-hexosaminidases remove terminal beta-glycosidically bound N-acetylhexosamine residues from a number of glycoconjugates. Three different isozymes composed of two noncovalently linked subunits alpha and beta exist: Hex A (alphabeta), Hex B (betabeta), and Hex S (alphaalpha). While the role of Hex A and B for the degradation of several anionic and neutral glycoconjugates has been well established, the physiological significance of labile Hex S has remained unclear. However, the striking accumulation of anionic oligosaccharides in double knockout mice totally deficient in hexosaminidase activity but not in mice expressing Hex S (Sango, K., McDonald, M. P., Crawley, J. N., Mack, M. L., Tifft, C.J., Skop, E., Starr, C. M., Hoffmann, A., Sandhoff, K., Suzuki, K., and Proia, R. L., (1996) Nat. Genet. 14, 348-352) prompted us to reinvestigate the substrate specificity of Hex S. To identify physiological substrates of Hex S, anionic and neutral oligosaccharides excreted in the urine of the double knockout mice were isolated and analyzed. Using ESI-MS/MS and glycosidase digestion the anionic glycans were identified as products of incomplete dermatan sulfate degradation whereas the neutral storage oligosaccharides were found to be fragments of N-glycan degradation. In vitro, recombinant Hex S was highly active on water-soluble and amphiphilic glycoconjugates including artificial substrates, sulfated GAG fragments, and the sulfated glycosphingolipid SM2. Hydrolysis of membrane-bound SM2 by the recombinant Hex S was synergistically stimulated by the GM2 activator protein and the lysosomal anionic phospholipid bis(monoacylglycero)phosphate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Chondroitin Sulfates, http://linkedlifedata.com/resource/pubmed/chemical/Dermatan Sulfate, http://linkedlifedata.com/resource/pubmed/chemical/G(M2) Activator Protein, http://linkedlifedata.com/resource/pubmed/chemical/Glycolipids, http://linkedlifedata.com/resource/pubmed/chemical/Hexosaminidase A, http://linkedlifedata.com/resource/pubmed/chemical/Hexosaminidase B, http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Monoglycerides, http://linkedlifedata.com/resource/pubmed/chemical/Polysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Water, http://linkedlifedata.com/resource/pubmed/chemical/beta-N-Acetylhexosaminidases, http://linkedlifedata.com/resource/pubmed/chemical/bis(monoacylglyceryl)phosphate
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2562-72
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11707436-Animals, pubmed-meshheading:11707436-Carbohydrate Sequence, pubmed-meshheading:11707436-Cell Line, pubmed-meshheading:11707436-Chondroitin Sulfates, pubmed-meshheading:11707436-Chromatography, Thin Layer, pubmed-meshheading:11707436-Dermatan Sulfate, pubmed-meshheading:11707436-G(M2) Activator Protein, pubmed-meshheading:11707436-Glycolipids, pubmed-meshheading:11707436-Hexosaminidase A, pubmed-meshheading:11707436-Hexosaminidase B, pubmed-meshheading:11707436-Humans, pubmed-meshheading:11707436-Hydrogen-Ion Concentration, pubmed-meshheading:11707436-Hydrolysis, pubmed-meshheading:11707436-Insects, pubmed-meshheading:11707436-Kidney, pubmed-meshheading:11707436-Kinetics, pubmed-meshheading:11707436-Lysophospholipids, pubmed-meshheading:11707436-Lysosomes, pubmed-meshheading:11707436-Mice, pubmed-meshheading:11707436-Mice, Knockout, pubmed-meshheading:11707436-Models, Chemical, pubmed-meshheading:11707436-Molecular Sequence Data, pubmed-meshheading:11707436-Monoglycerides, pubmed-meshheading:11707436-Polysaccharides, pubmed-meshheading:11707436-Protein Binding, pubmed-meshheading:11707436-Protein Processing, Post-Translational, pubmed-meshheading:11707436-Proteins, pubmed-meshheading:11707436-Rats, pubmed-meshheading:11707436-Recombinant Proteins, pubmed-meshheading:11707436-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:11707436-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:11707436-Substrate Specificity, pubmed-meshheading:11707436-Time Factors, pubmed-meshheading:11707436-Water, pubmed-meshheading:11707436-beta-N-Acetylhexosaminidases
pubmed:year
2002
pubmed:articleTitle
Physiological substrates for human lysosomal beta -hexosaminidase S.
pubmed:affiliation
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't