The INDIVIDUALIST

A Wiki about biochemical individuality

Nutrigenomics

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Description

The Lewis system involves genetically variable antigens in the body fluids and only secondarily are the antigens absorbed to red cells. The last step in the biosynthesis of Lewis antigen, the addition of a fucose to precursor polysaccharides, can be catalyzed by at least several types of alpha-3-fucosyltransferases: FUT1, or Bombay (211100), FUT2, or secretor (182100), FUT3, or Lewis, and FUT4, which is the myeloid form of alpha-3-fucosyltransferase (104230).

Gene function

Boren et al. (1) determined that the Lewis(b) antigen, Le(b), is an epithelial receptor for H. pylori (see 600263). The H. pylori adhesin that binds Lewis(b) is BabA, which is encoded by babA2, a strain-specific gene (Peek, 2003). H. pylori strains that are isolated from patients with gastric cancer more commonly possess this gene than do strains isolated from patients with gastritis alone. 30 PubMed Neighbors

Grollman et al. (2 ) showed that Lewis-negative women lack a specific fucosyltransferase which is present in the milk of Lewis-positive women. The enzyme is apparently required for synthesis of the structural determinants of both Lewis (a) and Lewis (b) specificity. The same enzyme is involved in the synthesis of milk oligosaccharides, because 2 oligosaccharides containing the relevant linkage were absent from the milk of Lewis-negative women. Grubb (3) provided the ingenious interpretation of the interactions between the Les locus determining presence/absence of Lewis substance in the saliva and on red cells and the Secretor locus determining secretion of ABH blood group substances in the saliva and Le(a) or Le(b) expression in red cells

Abstracts

Promoter analysis of the human alpha1,3/4-fucosyltransferase gene (FUT III)

Biochim Biophys Acta. 2005 Oct 15;1731:66-73 Anna Dabrowska, Dagmara Baczyńska, Katarzyna Widerak, Anna Laskowska, Maciej Ugorski alpha1,3/4-Fucosyltransferase (FUT3) is involved in the synthesis of sialyl Le(a) tetrasaccharide, a tumor-associated carbohydrate antigen. Fucosyltransferases are thought to be important regulatory enzymes in the synthesis of fucosylated structures. However, there are conflicting data on the role of FUT3 in the synthesis of this carbohydrate structure and more studies on the regulation of FUT III gene expression are needed. Therefore, as first step, the promoter of FUT III gene was cloned and characterized. Sequencing data showed the absence of TATA, CAAT, and GC boxes, but many binding sites for transcription factors, previously described in colon cancer cells, were identified. Analysis of enhancer and silencing elements of deletion mutants revealed the presence of basal promoter elements of the FUT III gene in the region -636 to -674 bp from the translation initiation site, and positive and negative regulatory elements within the -674 bp to -854 bp and -854 to -1220 regions, respectively. 5'-RACE analysis showed the presence of two transcripts with 5'-ends localized within the exon A. The 5'-end of the longer transcript extended -229 nucleotides from the translation start codon and contained a sequence corresponding to an Inr element, localizing the putative transcription initiation site within this sequence. The strong correlation between the promoter activity of the FUT III gene and the high expression of sialyl Le(a) observed in different colon carcinoma cell lines seem to confirm the important regulatory role of FUT3 in the synthesis of sialyl Le(a).

Influence of the combined ABO, FUT2, and FUT3 polymorphism on susceptibility to Norwalk virus attachment

J Infect Dis. 2005 Sep 15;192:1071-7 Séverine Marionneau, Fabrice Airaud, Nicolai V Bovin, Jacques Le Pendu, Nathalie Ruvoën-Clouet The binding of Norwalk virus (NV) recombinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. Blood group B saliva was poorly recognized, whereas binding to blood group O saliva was higher and binding to blood group A saliva was highest. Transfection of either blood group A or B enzyme into H epitope-expressing cells showed that masking of H epitopes by the A and B antigens blocked the attachment of NV capsids. The high level of binding to blood group A secretor saliva could be explained by an optimal H type 1 ligand density, which was lower than that in blood group O saliva and much higher than that in blood group B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and binding to a synthetic probe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.

Links

References


1. Boren, T.; Falk, P.; Roth, K. A.; Larson, G.; Normark, S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 262: 1892-1895, 1993.

2. Grollman, E. F.; Kobata, A.; Ginsburg, V. : An enzymatic basis for Lewis blood types in man. J. Clin. Invest. 48: 1489-1494, 1969

3. Grubb, R. Zur Genetik des Lewis-Systems. Naturwissenschaften 21: 560-561, 1953.

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