Document Detail


Hyaluronan catabolism: a new metabolic pathway.
MedLine Citation:
PMID:  15503855     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new pathway of intermediary metabolism is described involving the catabolism of hyaluronan. The cell surface hyaluronan receptor, CD44, two hyaluronidases, Hyal-1 and Hyal-2, and two lysosomal enzymes, beta-glucuronidase and beta-N-acetylglucosaminidase, are involved. This metabolic cascade begins in lipid raft invaginations at the cell membrane surface. Degradation of the high-molecular-weight extracellular hyaluronan occurs in a series of discreet steps generating hyaluronan chains of decreasing sizes. The biological functions of the oligomers at each quantum step differ widely, from the space-filling, hydrating, anti-angiogenic, immunosuppressive 10(4)-kDa extracellular polymer, to 20-kDa intermediate polymers that are highly angiogenic, immuno-stimulatory, and inflammatory. This is followed by degradation to small oligomers that can induce heat shock proteins and that are anti-apoptotic. The single sugar products, glucuronic acid and a glucosamine derivative are released from lysosomes to the cytoplasm, where they become available for other metabolic cycles. There are 15 g of hyaluronan in the 70-kg individual, of which 5 g are cycled daily through this pathway. Some of the steps in this catabolic cascade can be commandeered by cancer cells in the process of growth, invasion, and metastatic spread.
Authors:
Robert Stern
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  European journal of cell biology     Volume:  83     ISSN:  0171-9335     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-10-26     Completed Date:  2005-01-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  317-25     Citation Subset:  IM    
Affiliation:
Department of Pathology, School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, S-564, San Francisco, CA 94143-0511, USA. rstern@itsa.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD44 / immunology,  metabolism*
Apoptosis / immunology,  physiology
Glucosamine / immunology,  metabolism
Glucuronic Acid / immunology,  metabolism
Glycoside Hydrolases / immunology,  metabolism*
Humans
Hyaluronic Acid / immunology,  metabolism*
Lysosomes / metabolism*
Membrane Microdomains / immunology,  metabolism*
Mice
Mucolipidoses / metabolism
Neoplasms / immunology,  metabolism
Neovascularization, Physiologic / immunology,  physiology
Chemical
Reg. No./Substance:
0/Antigens, CD44; 3416-24-8/Glucosamine; 576-37-4/Glucuronic Acid; 9004-61-9/Hyaluronic Acid; EC 3.2.1.-/Glycoside Hydrolases

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