Disease relevance of UGT8

• Using a GalC expressing cell line, human oligodendroglioma (HOG), one which does not express GalC, human neuroblastoma (LAN-5), we previously demonstrated that the human CGT (hCGT) gene promoter functions in a cell-specific manner [1].
• The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia [2].
• As part of the search for new antimalarial drugs, a screening program was developed using sensitive and chlorguanide triazine (CGT, cycloguanil) resistant strains of the folate-requiring bacteria, Streptococcus faecium durans, Lactobacillus casei, and Pediococcus cerevisiae [3].
• In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred [4].
• To study the effect of these two tandems on the expression of hIFN alpha 1 in E. coli, four new gene variants were designed to contain preferential Arg codons (CGT) substituted for the rare AGG codons in either the first, the second or both AGG tandems [5].

Psychiatry related information on UGT8

• Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them [6].
• Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation [6].

High impact information on UGT8

• In this article, we correlate these two phenotypes and show that both NCP1 and CGT mutants develop large swellings accompanied by cytoskeletal disorganization and degeneration in the axons of cerebellar Purkinje neurons [7].
• Sequencing of all coding exons of the M2 gene revealed it was identical to the common M1(Val213) gene except for two bases (M1(Val213) CGT Arg101, M2 CAT His101; M1(Val213) GAA Glu376 M2 GAC Asp376) [8].
• This heterozygous mutation encodes both Cys (TGT) and Arg (CGT) at residue 153 [9].
• DNA sequence analysis in the proband showed a novel missense mutation substituting Cys (TGT) for Arg474 (CGT) that is a highly conserved amino acid residue among the related proteins [10].
• We found a G to A base substitution in the 22nd codon (CAT for CGT), which changes the normal arginine to a histidine [11].

Chemical compound and disease context of UGT8

• Analysis of a subject with incomplete testicular feminization revealed a single substitution (CGT --> CAT) at nucleotide 2675 of exon 7, resulting in the conversion of an arginine at amino acid 840 to a histidine [12].
• A selective medium (CGT medium), containing clindamycin, gentamicin, potassium tellurite and amphotericin B in 5% horse-blood agar, allowed unimpaired growth of almost all strains of Pasteurella multocida, and P pneumotropica, while inhibiting other bacteria that might be encountered in upper respiratory tract secretions [13].
• The point mutation from CGT (Arg) to TGT (Cys) at codon 201 was detected in 21 pituitary tumors, but the point mutation from CAG (Gln) to CTG (Leu) at codon 227 of the Gs alpha gene was found in only 1 tumor [14].

Biological context of UGT8

• However, UGT2A3 and those of the UGT2B (six exons), UGT3 (seven exons) and UGT8 gene families (five or six exons) do not share exons and most likely were derived by a process of duplication of all exons in the gene [15].
• The CGT locus was mapped to the distal region of human chromosome 4, band q26 [16].
• Transcriptional regulation of the human UDP-galactose:ceramide galactosyltransferase (hCGT) gene expression: functional role of GC-box and CRE [1].
• A novel amino acid substitution in the reactive site of a congenital variant antithrombin. Antithrombin pescara, ARG393 to pro, caused by a CGT to CCT mutation [17].
• Marked zinc activation of ester hydrolysis by a mutation, 67-His (CAT) to Arg (CGT), in the active site of human carbonic anhydrase I [18].

Anatomical context of UGT8

• The CGT gene therefore is important in the differentiation program of the oligodendrocyte lineage [16].
• UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.45) is a key enzyme in the biosynthetic pathway of galactocerebroside (GalC), the most abundant glycolipid in myelin [1].
• UDP-galactose ceramide galactosyltransferase, CGT, EC 2.4.1.45, is the key enzyme in the biosynthesis of cerebrosides and sulfatides, which are the most abundant glycosphingolipids in the myelin of the central nervous system and the peripheral nervous system [19].
• We have found that CGT is induced during keratinocyte culture differentiation coincident with increased GlcCer content and the appearance of lamellar granules [20].
• The present study further characterizes the properties of N-alk(en)ylated DNJs, and demonstrates that increasing the length of the side chain is a simple way of improving imino sugar retention and therefore inhibitory efficacy for CGT in cultured cells [21].

Associations of UGT8 with chemical compounds

• The human gene CGT encoding the UDP-galactose ceramide galactosyl transferase (cerebroside synthase): cloning, characterization, and assignment to human chromosome 4, band q26 [16].
• A homozygous and heterozygous two-base mutation (CCC to CGT) created the HUG-Br1P387R mutant of the major bilirubin transferase in 2 different Crigler-Najjar type I patients, B.G. and G.D., respectively [22].
• Apolipoprotein (apo) E-4Philadelphia is a double mutant of apoE in which residue 13 of the mature protein, glutamic acid (GAG), is replaced by lysine (AAG) and amino acid 145, arginine (CGT), is converted to cysteine (TGT) [23].
• Sequence analyses show short spacers between the CAT repeats consisting of closely related trinucleotides, primarily CGT [24].
• A point mutation was discovered that changed codon 65 from arginine (CGT) to histidine (CAT) in one allele [25].

Other interactions of UGT8

• We report here three high-density maps of variations found among 48 Japanese individuals in three uridine diphosphate glycosyltransferase (UGT) genes, UGT2A1, UGT2B15, and UGT8 [26].
• The organization of the CGT gene and of the UGT (uridylglucuronosyltransferases) gene family suggests a correlation to functional domains of the encoded proteins [16].
• The activity of cerebroside synthase (UDP-glucose: ceramide glucosyltransferase) was found in the microsomal fraction of radish hypocotyls, and was studied [27].

Analytical, diagnostic and therapeutic context of UGT8

• Northern blot hybridization was used to determine the length of CGT mRNA and Southern blot hybridization was used to determine the number of homologous genes [28].
• DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65 [29].
• The CGT was purified 526-fold from the cytosolic fraction of UV-irradiated cell cultures by ion-exchange chromatography on diethylaminoethyl (DEAE)-Sephacel, affinity chromatography on Blue Sepharose CL-6B, gel permeation chromatography on Sephadex G-75 and elution from the gel matrix after non-dissociating PAGE [30].
• Northern blot analysis of CGT revealed increased expression of it in Z65 cells compared with that in CHO-K1 cells, which probably caused the simultaneous increase in GM3 [31].
• These two pairs of consecutive AGG codons were successively replaced with the major synonymous codon CGT by site-directed mutagenesis [32].

References