Document Detail


Acid ceramidase and human disease.
MedLine Citation:
PMID:  17064658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acid ceramidase (N-acylsphingosine deacylase, EC 3.5.1.23; AC) is the lipid hydrolase responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. The enzymatic activity was first identified over four decades ago, and is deficient in the inherited lipid storage disorder, Farber Lipogranulomatosis (Farber disease). Importantly, AC not only hydrolyzes ceramide into sphingosine, but also can synthesize ceramide from sphingosine and free fatty acids in vitro and in situ. This "reverse" enzymatic activity occurs at a distinct pH from the hydrolysis ("forward") reaction (6.0 vs. 4.5, respectively), suggesting that the enzyme may have diverse functions within cells dependent on its subcellular location and the local pH. Most information concerning the role of AC in human disease stems from work on Farber disease. This lipid storage disease is caused by mutations in the gene encoding AC, leading to a profound reduction in enzymatic activity. Recent studies have also shown that AC activity is aberrantly expressed in several human cancers, and that the enzyme may be a useful cancer drug target. For example, AC inhibitors have been used to slow the growth of cancer cells, alone or in combination with other established, anti-oncogenic treatments. Aberrant AC activity also has been described in Alzheimer's disease, and overexpression of AC may prevent insulin resistant (Type II) diabetes induced by free fatty acids. Current information concerning the biology of this enzyme and its role in human disease is reviewed within.
Authors:
Jae-Ho Park; Edward H Schuchman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2006-09-01
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1758     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2133-8     Citation Subset:  IM    
Affiliation:
Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14-20A, New York, NY 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease*
Galactosylgalactosylglucosylceramidase / genetics,  metabolism*
Humans
Mice
Mice, Knockout
Recombinant Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
R01 DK 54830/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Recombinant Proteins; EC 3.2.1.47/Galactosylgalactosylglucosylceramidase

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