Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle.

Niimi, M.; Ogawara, T.; Yamashita, T.; Yamamoto, Y.; Ueyama, A.; Kambe, T.; Okamoto, T.; Ban, T.; Tamanoi, H.; Ozaki, K.; Fujiwara, T.; Fukui, H.; Takahashi, E.; Kyushiki, H.; Tanigami, A.

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.

GLUTAMINE; ENZYMES; HEXOSAMINES; INSULIN resistance

Journal of Human Genetics, 2001, Vol 46, Issue 10, p566

1434-5161

Academic Journal

10.1007/s100380170022