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

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeHaven, J. E. Articles by Buse, M. G. Search for Related Content PubMed PubMed Citation Articles by DeHaven, J. E. Articles by Buse, M. G. Social Bookmarking                What's this?

A Novel Variant of Glutamine

Fructose-6-Phosphate Amidotransferase-1 (GFAT1) mRNA Is Selectively Expressed in Striated Muscle

¹ Medicine, Division of Endocrinology, Diabetes and Medical Genetics, and
² Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina

Glutamine:fructose-6-phosphate  amidotransferase(GFAT) is the rate-limiting enzyme of the hexosamine synthesis pathway. Products of this pathway have been implicated in insulin resistance and glucose toxicity. GFAT1 is ubiquitous, whereas GFAT2 is expressed mainly in the central nervous system. In the course of developing a competitive reverse transcriptase–polymerase chain reaction assay, we noted that GFAT1 cDNA from muscle but not from other tissues migrated as a doublet. Subsequent cloning and sequencing revealed two GFAT1 mRNAs in both mouse and human skeletal muscles. The novel GFAT1 mRNA (GFAT1Alt [muscle selective variant of GFAT1]) is likely a splice variant. It is identical to GFAT1 except for a 48 or 54 bp insert in the mouse and human, respectively, at nucleotide position 686 of the coding sequence, resulting in a 16 or 18 amino acid insert at position 229 of the protein. GFAT1Alt is the predominant GFAT1 mRNA in mouse hindlimb muscle, is weakly expressed in the heart, and is undetectable in the brain, liver, kidney, lung, intestine, spleen, and 3T3-L1 adipocytes. In humans, it is strongly expressed in skeletal muscle but not in the brain. GFAT1 and GFAT1Alt expressed by recombinant adenovirus infection in COS-7 cells displayed robust enzyme activity and kinetic differences. The apparent K_m of GFAT1Alt for fructose-6-phosphate was approximately twofold higher than that of GFAT1, whereas K_i for UDP-N-acetylglucosamine was approximately fivefold lower. Muscle insulin resistance is a hallmark and predictor of type 2 diabetes. Variations in the expression of GFAT isoforms in muscle may contribute to predisposition to insulin resistance.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. P.K. Ng, W. H. Walker, K.-S. Chia, S. Choo, J. H. Warram, and A. S. Krolewski Scrutiny of the Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) Locus Reveals Conserved Haplotype Block Structure not Associated With Diabetic Nephropathy Diabetes, March 1, 2004; 53(3): 865 - 869. [Abstract] [Full Text] [PDF]

				C. Weigert, K. Klopfer, C. Kausch, K. Brodbeck, M. Stumvoll, H. U. Haring, and E. D. Schleicher Palmitate-Induced Activation of the Hexosamine Pathway in Human Myotubes: Increased Expression of Glutamine:Fructose-6-Phosphate Aminotransferase Diabetes, March 1, 2003; 52(3): 650 - 656. [Abstract] [Full Text] [PDF]

				K. O. Broschat, C. Gorka, J. D. Page, C. L. Martin-Berger, M. S. Davies, H.-c. Huang, E. A. Gulve, W. J. Salsgiver, and T. P. Kasten Kinetic Characterization of Human Glutamine-fructose-6-phosphate Amidotransferase I. POTENT FEEDBACK INHIBITION BY GLUCOSAMINE 6-PHOSPHATE J. Biol. Chem., April 19, 2002; 277(17): 14764 - 14770. [Abstract] [Full Text] [PDF]