CONICET | Buscador de Institutos y Recursos Humanos

Glycosylated D-galactose is widely distributed in nature. Less common, L-galactose was found in snail and plant galactans. At difference with the most abundant monosaccharide, D-glucose, D-galactose may be found in pyranosic and furanosic configurations. In the animal kingdom, free D-galactose is not present but is a common constituent of glycoproteins and glycolipids, always as pyranose. In fact, D-galactose is incorporated into human milk oligosaccharides in larger quantities than glucose. The galactosyltransferase links galactose to glucose to form lactose, the core for human milk oligosaccharides (HMO). Interestingly, the furanose form has been identified in important human pathogens like Mycobacterium tuberculosis, Aspergillus fumigatus and Trypanosoma cruzi, the agent of Chagas disease. In both configurations, the beta-anomer predominates in the glycans. The absence of galactofuranose (Galf) in mammals and the important role that Galf-containing molecules play in host cell recognition led to the enzymes involved in the Galf metabolic pathways as targets for the development of drugs. Both, Galp and Galf must be activated as the nucleotides UDP-Galp and UDP-Galf for their incorporation into glycans. The nucleotide precursor for L-galactose is GDP-L-galactose, which is formed from GDP-mannose by the action of a 3,5-epimerase. Also, whereas UDP-Galp may be synthesized from the free monosaccharides galactose or glucose, in the latter case through the action of a UDP-Glc-4-epimerase, UDP-Galf is produced from UDP-Galp by the action of a unique enzyme, UDP-Galp mutase (UGM), which catalyzes its conversion into UDP-Galf. In the last two decades several laboratories have been committed to understand the mechanism of action of UGM and its properties. The achievements in this area are presented in this chapter.