The metabolism of 6-deoxyhexoses in bacterial and animal cells

L-fucose and L-rhamnose are two 6-deoxyhexoses naturally occurring in sever al complex carbohydrates. In prokaryotes both of them are found in polysacc harides of the cell wall, while in animals only L-fucose has been described , which mainly participates to the structure of glycoconjugates, either in the cell membrane or secreted in biological fluids, such as ABH blood group s and Lewis system antigens. L-fucose and L-rhamnose are synthesized by two de novo biosynthetic pathways starting from GDP-D-mannose and dTDP-D-gluco se, respectively, which share several common features. The first step for b oth pathways is a dehydration reaction catalyzed by specific nucleotide-sug ar dehydratases. This leads to the formation of unstable 4-keto-6-deoxy int ermediates, which undergo a subsequent epimerization reaction responsible f or the change from D- to L-conformation, and then a NADPH-dependent reducti on of the 4-keto group, with the consequent formation of either GDP-L-fucos e or dTDP-L-rhamnose. These compounds are then the substrates of specific g lycosyltransferases which are responsible for insertion of either L-fucose or L-rhamnose in the corresponding glycoconjugates. The enzyme involved in the first step of GDP-L-fucose biosynthesis in E. coli, i.e., GDP-D-mannose 4,6 dehydratase, has been recently expressed as recombinant protein and ch aracterized in our laboratory. We have also cloned and fully characterized a human protein, formerly named FX, and an E. coli protein, WcaG, which dis play both the epimerase and the reductase activities, thus indicating that only two enzymes are required for GDP-L-fucose production. Fucosylated comp lex glycoconjugates at the cell surface can then be recognized by specific counter-receptors in interacting cells, these mechanisms initiating importa nt processes including inflammation and metastasis. The second pathway star ting from dTDP-D-glucose leads to the synthesis of antibiotic glycosides or , alternatively, to the production of dTDP-L-rhamnose. While several sets o f data are available on the first enzyme of the pathway, i.e., dTDP-D-gluco se dehydratase, the enzymes involved in the following steps still need to b e identified and characterized. (C) Societe francaise de biochimie et biolo gie moleculaire / Elsevier, Paris.