title: UDP-N-acetylglucosamine 4'-epimerase from the intestinal protozoan Giardia intestinalis lacks UDP-glucose 4'-epimerase activity.
abstract: The protozoan parasite Giardia intestinalis has a simple life cycle consisting of an intestinal trophozoite stage and an environmentally resistant cyst stage. The cyst is formed when a trophozoite encases itself within an external filamentous covering, the cyst wall, which is crucial to the cyst's survival outside of the host. The filaments in the cyst wall consist mainly of a beta (1-3) polymer of N-acetylgalactosamine. Its precursor, UDP-N-acetylgalactosamine, is synthesized from fructose 6-phosphate by a pathway of five inducible enzymes. The fifth, UDP-N-acetylglucosamine 4'-epimerase, epimerizes UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine reversibly. The epimerase of G. intestinalis lacks UDP-glucose/UDP-galactose 4'-epimerase activity and shows characteristic amino acyl residues to allow binding of only the larger UDP-N-acetylhexosamines. While the Giardia epimerase catalyzes the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine, the reverse reaction apparently is favored. The enzyme has a higher Vmax and a smaller Km in this direction. Therefore, an excess of UDP-N-acetylglucosamine is required to drive the reaction towards the synthesis of UDP-N-acetylgalactosamine, when it is needed for cyst wall formation. This forms the ultimate regulatory step in cyst wall biosynthesis.
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio 44115, USA.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lopez
authors.forename: Keriman
authors.initials: K
authors.lastname: Sener
authors.forename: Julia
authors.initials: J
authors.lastname: Trosien
authors.forename: Edward L
authors.initials: EL
authors.lastname: Jarroll
authors.forename: Harry
authors.initials: H
authors.lastname: van Keulen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002238:Carbohydrate Epimerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016829:Giardia lamblia / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D053058:Trophozoites / Q000166:cytology / Q000378:metabolism; D014534:UDPglucose 4-Epimerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000378:metabolism; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D014537:Uridine Diphosphate N-Acetylglucosamine; D014536:Uridine Diphosphate N-Acetylgalactosamine; D002238:Carbohydrate Epimerases; C023223:UDP-N-acetylglucosamine 4-epimerase; D014534:UDPglucose 4-Epimerase