Disease relevance of GBGT1

• A synthetic peptide corresponding to the human MUC2 tandem repeat unit was glycosylated in vitro using UDP-GalNAc and extracts of colonic adenocarcinoma and paired normal mucosa, followed by fractionation of the products by reverse phase high-performance liquid chromatography [1].
• The mammalian form of the enzyme, unlike its Escherichia coli counterpart, can also interconvert UDP-GalNAc and UDP-GlcNAc [2].
• Animal studies suggest that overactivity of the hexosamine pathway, resulting in increased UDP-hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc)] is an important mechanism by which hyperglycemia causes insulin resistance [3].
• Sequencing of some of the tumor-specific altered regions indicated that they code for regions of UDP-GalNAc and hRAD 17 genes, which were lost (deleted) in oral cancer [4].
• A synthetic peptide corresponding to the human MUC2 tandem repeat domain containing 14 Thr residues was glycosylated in vitro using UDP-GalNAc and microsomal membranes of the colorectal cancer cell line, LS180 [5].

High impact information on GBGT1

• Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal/UDP-GalNAc 4-epimerase deficient mutant [6].
• When ldlD cells are grown in glucose-based media, they cannot synthesize enough UDP-galactose and UDP-GalNAc to allow normal synthesis of glycolipids and glycoproteins [6].
• The deduced amino acid sequence of FS demonstrates extensive identity to three previously cloned glycosyltransferases, including the enzymes responsible for synthesis of histo-blood group A and B antigens [7].
• Thus, the FS cDNA is a novel member of the histo-blood group ABO gene family that encodes glycosyltransferases with related but distinct substrate specificity [7].
• The conformation with the highest occupancy opens up the active site to accommodate the larger A-specific donor, UDP-GalNAc, accounting for the dual specificity [8].

Chemical compound and disease context of GBGT1

• Unlike that observed for the protein isolated from Escherichia coli, the human enzyme can also turn over UDP-GlcNAc to UDP-GalNAc and vice versa [9].
• Comparing the human GALE- and E. coli GALE-expressing cells, we found that although GALE activity toward both substrates was required to restore metabolic balance, UDP-GalNAc activity was not required for cell proliferation in the presence of otherwise cytostatic concentrations of galactose [10].
• The acute-phase response of alpha 1-acid glycoprotein was accompanied by increased liver pools of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) and increased liver activities of glucosamine-6-phosphate synthase and UDP-GlcNAc 2-epimerase [11].
• Augmentation of UDP-GalNAc: Fucalpha1-2Gal alpha1-3 N-acetylgalactosaminyl transferase activity in nitrosamine-induced hamster pancreatic cancers [12].

Biological context of GBGT1

• Reverse transcription polymerase chain reaction and Northern blotting demonstrated the presence of FS mRNA in all tissues examined [13].
• In contrast to the canine FS cDNA, transfection of COS-1 cells with the human FS cDNA resulted in no detectable FS enzyme activity [13].
• We investigated the effects of sodium monofluorophosphate (26 mg/day of fluoride) combined with 1000 mg of calcium (MFP-calcium-treated group), or of calcium alone (control), given for 18 months, on bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and midfemoral shaft (FS) in 48 patients with corticosteroid-induced osteoporosis [14].
• The enzymatic oxidation of uridine 5'-diphospho-alpha-D-galactose (UDP-Gal) and uridine 5'-diphospho-N-acetyl-alpha-D-galactosamine (UDP-GalNAc) with galactose oxidase was combined with a chemical biotinylation step involving biotin-epsilon-amidocaproylhydrazide in a one-pot synthesis [15].
• Isolation of a porcine UDP-GalNAc transferase cDNA mapping to the region of the blood group EAA locus on pig chromosome 1 [16].

Anatomical context of GBGT1

• In the present report, five oligopeptides [PTTTPITTTT(K), ITTTTTVTPT(K), TVTPTPTPTG(K), PTPTGTQTPT(K) and TQTPTTTPIT(K)] corresponding to portions of the MUC2 tandem repeat domain were synthesized, and incubated with UDP-N-acetyl-D-galactosamine (UDP-GalNAc) and detergent-soluble microsomes, prepared from the human colon carcinoma cell line LS174T [17].
• In order to examine the relationship between FG expression and Stx susceptibility, Vero cells were transfected with the three FS orthologues or a vector control [18].
• Lepidopteran insect cell lines derived from Trichoplusia ni, Spodoptera frugiperda, and Mamestra brassicae were found to express a beta 1-->4- N-acetylgalactosaminyltransferase (beta 4-GalNAcT) that catalyzes the transfer of GalNAc from UDP-GalNAc to oligosaccharides and glycoproteins carrying a terminal beta-linked GlcNAc residue [19].
• Erythrocyte membranes were labeled with radioactive N-acetylgalactosamine (GalNAc) from UDP-GalNAc using a purified A-blood-group gene-specified transfered of GalNAc [20].
• Uridine-5'-diphospho-N-acetylgalactosamine (UDP-GalNAc) is required in the formation of the outer filamentous wall of Giardia and is synthesized by inducible enzymes in the cytosol of encysting trophozoites [21].

Associations of GBGT1 with chemical compounds

• Despite the high degree of sequence similarity among the transferases, we demonstrate that the FS cDNA encodes an enzyme capable of synthesizing Forssman glycolipid, and demonstrates no GalNAc or Gal transferase activity when closely related substrates are examined [7].
• These studies have revealed that, indeed, this simple mutation did confer UDP-GalNAc/UDP-GlcNAc converting activity to the bacterial enzyme with minimal changes in its three-dimensional structure [2].
• This study revealed that the enzyme binds several UDP-activated sugars, including UDP-Glc, UDP-GlcNAc, and UDP-GalNAc [22].
• Identification and modification of the uridine-binding site of the UDP-GalNAc (GlcNAc) pyrophosphorylase [23].
• In addition, a ganglioside with identical chromatographic mobility can be obtained by the enzymatic transfer of GalNAc from UDP-GalNAc to sialosylparagloboside using a microsomal preparation from human kidney [24].

Enzymatic interactions of GBGT1

• Initial glycosylation of mucin-type O-linked protein is catalysed by one of the UDP-GalNAc: polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3) [25].
• Our results showed that GgOse3Cer-II3-sulfate could be synthesized from lactosylceramide 3'-sulfate and UDP-GalNAc catalyzed by N-acetylgalactosaminyltransferase prepared from rat brain (Dicesare, J. L., and Dain, J. A. (1971) Biochim. Biophys. Acta 231, 385-393) [26].

Other interactions of GBGT1

• GalNAc-T1 and -T3 showed strict donor substrate specificities for UDP-GalNAc, whereas GalNAc-T2 also utilized UDP-Gal with one peptide acceptor substrate [27].
• Studies on the order and site specificity of GalNAc transfer to MUC1 tandem repeats by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase from milk or mammary carcinoma cells [28].
• GALNT3 that encodes the UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferase-T3 (GalNAc-T3), was recently identified and mapped to a region 5-25 cM from D2S152 [29].
• The UDP-GalNAC: polypeptide N-acetylgalactosaminyltransferase activity in microsomal fractions from these cells did not change upon NCCM treatment [30].
• A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase specificity from UDP-GalNAc to UDP-GlcNAc [31].

Analytical, diagnostic and therapeutic context of GBGT1

• Cloning of the FS cDNA will allow a detailed dissection of the roles Forssman glycolipid plays in cellular differentiation, development, and malignant transformation [7].
• Before and after iv insulin treatment, insulin sensitivity was measured using a hyperinsulinemic euglycemic clamp, and a muscle biopsy was taken for measurement of UDP-GlcNAc, UDP-GalNAc, UDP-glucose, and UDP-galactose levels [3].
• The incubation products of these glycopeptides, microsome fractions of LS174T cells, and UDP-GalNAc were fractionated by reverse-phase HPLC and their structures were determined using MALDI-TOF MS and peptide sequencing [32].
• Highly significant alterations of phospholipid metabolite concentrations and UDP-hexoses (primarily UDP-GlcNAc and UDP-GalNAc) were observed as a function of the precursor concentrations, culture time or perfusion time [33].
• We isolated a rat cDNA clone and its human orthologue, which are most homologous to UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase 9, by homology-based PCR from brain [34].

References