Fucose metabolism

Marquardt, T, Brune, T, Luhn, K., etal., Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J. Pediatr. 134, 681-688 (1999). 

Reitman, M.L. Trowbridge, I.S. Komfeld, S. (1980) Mouse Lymphoma Cell Lines Resistant to Pea Lectin are Defective in Fucose Metabolism , Journal of Biological Chemistry, 215, 9900-6... 

Marquardt, T. Liihn, K. Srikrishna, G. Freeze, H.H. Harms, E. Vestweber, D. Fucose Therapy for Leukocyte Adhesion Deficiency Type II (LAD II). Blood 1999, 94, 3976-3985. Chan, J.Y. Nwokoro, N.A. Schachter, H. L-Fucose metabolism in mammals. The conversion of L-fucose to two moles of L-lactate, of L-galactose to L-lactate and glycerate, and of D-arabinose to L-lactate and glycollate. J. Biol. Chem. 1979, 254, 7060-7068. 

The importance of seleetins in humans is underscored by the discovery of a congenital disorder of fucose metabolism, termed leukocyte adhesion deficiency 2 (LAD-2) [49]. Because patients with LAD-2 lack fucosylated glycoconjugates, they do not express functional selectin ligands. Leukocytes from these patients do not tether to and roll on P- or E-selectin surfaces. Clinically, the patients have more infections, supporting the concept that the selectins have an important function in initiating recruitment of leukocytes. 

Another Arabidopsis mutant, murl, which lacks the ability to synthesize 1-fucose, possesses a defective gene encoding GDP-d-Man-4,6-dehydratase, a key enzyme in 1-fucose biosynthesis. Further analysis revealed that 1-Fuc is replaced by 1-Gal, a structurally similar monosaccharide, in the cell walls of this mutant with no adverse effects on plant physiology or metabolism (Rayon et al, 1999). Transgenic plants containing this mutation can also be used for foreign protein production. 

The object of this chapter is twofold to discuss aspects of the chemistry of the fucoses, especially developments in this field, and to consider their metabolism and biochemistry, and point out possible biological functions and medical applications of the fucoses and their compounds. 

Only, a few sugars are found in Nature in the form of both optical isomers (for example, galactose and arabinose). It is intriguing to speculate on the special conditions that determine the presence of the rarer form (for instance, the limiting of D-fucose to certain plant and microbial products), and on the specific pathways involved in their metabolism. 

The authors pointed out that such a metabolic pathway may complicate the results of biosynthetic studies in certain species, as it would provide a route for the oxidation of L-fucose and its eventual provision of carbon atoms to other sugars. This metabolic route does not occur in rats, but it is known215 that humans can oxidize L-[l-,4C]fucose to carbon dioxide. Only pig liver and kidney were found to contain appreciable levels of the major enzymes needed in this pathway, whereas heart, stomach, intestine, submaxillary gland, lung, and brain were deficient in or devoid of them. 

The metabolic degradation of D-fucose has been investigated in bacteria, and oxidative steps elucidated that closely resemble those undergone by the L enantiomer in the animal body. 

The metabolism of free L-fucose (6-deoxy-L-galac-tose), which is present in the diet and is also generated by degradation of glycoproteins, resembles the Entner-Doudoroff pathway of glucose metabolism (Eq. 17-18). Similar degradative pathways act on D-arabinose and L-galactose.60... 

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