Document Detail

Hyaluronan catabolism: a new metabolic pathway.
MedLine Citation:
PMID:  15503855     Owner:  NLM     Status:  MEDLINE    
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.
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    
Department of Pathology, School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, S-564, San Francisco, CA 94143-0511, USA.
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MeSH Terms
Antigens, CD44 / immunology,  metabolism*
Apoptosis / immunology,  physiology
Glucosamine / immunology,  metabolism
Glucuronic Acid / immunology,  metabolism
Glycoside Hydrolases / immunology,  metabolism*
Hyaluronic Acid / immunology,  metabolism*
Lysosomes / metabolism*
Membrane Microdomains / immunology,  metabolism*
Mucolipidoses / metabolism
Neoplasms / immunology,  metabolism
Neovascularization, Physiologic / immunology,  physiology
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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