GDP Mannose-4,6-Dehydratase (GMDS)

GMD catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans.The sequence of the predicted human protein is 61% identical to that of E. coli GMD. Northern blot analysis revealed that GMD is expressed as a 1.7-kb transcript in all tissues examined. human GMD cDNA complements the defect in Lec13, a Chinese hamster ovary cell line deficient in GMD activity. Using purified GMD and FX, the authors showed that the 2 proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro.