title: Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle.
abstract: Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.
authors.affiliation: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Niimi
authors.forename: T
authors.initials: T
authors.lastname: Ogawara
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Ueyama
authors.forename: T
authors.initials: T
authors.lastname: Kambe
authors.forename: T
authors.initials: T
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Ban
authors.forename: H
authors.initials: H
authors.lastname: Tamanoi
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: E I
authors.initials: EI
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Kyushiki
authors.forename: A
authors.initials: A
authors.lastname: Tanigami
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)