HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 10, 8035-8042, March 7, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/10/8035    most recent M212127200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luchansky, S. J. Articles by Bertozzi, C. R. Search for Related Content PubMed PubMed Citation Articles by Luchansky, S. J. Articles by Bertozzi, C. R. Social Bookmarking                      What's this?

GlcNAc 2-Epimerase Can Serve a Catabolic Role in Sialic Acid Metabolism^*

Sarah J. Luchansky, Kevin J. Yarema^§, Saori Takahashi^¶, and Carolyn R. Bertozzi^**§§

From the Departments of  Chemistry and  Molecular and Cell Biology and the ^** Howard Hughes Medical Institute, University of California, Berkeley, California 94720 and the  Center for Advanced Materials, Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and the ^¶ Department of Bioengineering, Akita Research Institute of Food and Brewing, 4-26 Sanuki, Arayamachi, Akita 010-1623, Japan

Sialic acid is a major determinant of carbohydrate-receptor interactions in many systems pertinent to human health and disease. N-Acetylmannosamine (ManNAc) is the first committed intermediate in the sialic acid biosynthetic pathway; thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. UDP-GlcNAc 2-epimerase and GlcNAc 2-epimerase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively. Whereas the former enzyme has been shown to direct metabolic flux toward sialic acid in vivo, the function of the latter enzyme is unclear. Here we study the effects of GlcNAc 2-epimerase expression on sialic acid production in cells. A key tool we developed for this study is a cell-permeable, small molecule inhibitor of GlcNAc 2-epimerase designed based on mechanistic principles. Our results indicate that, unlike UDP-GlcNAc 2-epimerase, which promotes biosynthesis of sialic acid, GlcNAc 2-epimerase can serve a catabolic role, diverting metabolic flux away from the sialic acid pathway.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. Maliekal, D. Vertommen, G. Delpierre, and E. Van Schaftingen Identification of the sequence encoding N-acetylneuraminate-9-phosphate phosphatase Glycobiology, February 1, 2006; 16(2): 165 - 172. [Abstract] [Full Text] [PDF]

				S. E. Sparks, C. Ciccone, M. Lalor, E. Orvisky, R. Klootwijk, P. J. Savelkoul, M. C. Dalakas, D. M. Krasnewich, W. A. Gahl, and M. Huizing Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy Glycobiology, November 1, 2005; 15(11): 1102 - 1110. [Abstract] [Full Text] [PDF]

				Y. Hong and P. Stanley Lec3 Chinese Hamster Ovary Mutants Lack UDP-N-acetylglucosamine 2-Epimerase Activity Because of Mutations in the Epimerase Domain of the Gne Gene J. Biol. Chem., December 26, 2003; 278(52): 53045 - 53054. [Abstract] [Full Text] [PDF]