Passage
Dystroglycan (Dg) is a transmembrane protein that mediates interactions between the cytoskeleton and the extracellular matrix (ECM) . It binds the ECM protein laminin in an interaction that is required for intercellular communication and muscle membrane structural stability. The Dg-laminin interaction is facilitated by a long carbohydrate chain called an O-mannosyl glycan, which is covalently linked to Dg (Figure 1) .
Figure 1 Schematic of interaction between Dg and laminin, mediated by the Dg-linked O-mannosyl glycanThe O-mannosyl glycan is added to Dg by a series of enzymes called glycosyltransferases. The first enzyme in this series, protein O-mannosyltransferase (POMT) , attaches D-mannose to the hydroxyl groups of serine and threonine residues in an α-linkage through the anomeric carbon. The next sugar in the chain then forms a β-1,4 linkage to the mannose residue, followed by several more steps to produce the full glycan. Genetic inactivation of any of the enzymes in the pathway results in an incomplete glycan and failure to bind laminin, and is the underlying cause of several severe forms of muscular dystrophy known as dystroglycanopathies.Researchers investigating dystroglycanopathies recently discovered the functions of two enzymes in the pathway: protein O-mannose kinase (POMK) and fukutin. POMK phosphorylates Dg-linked mannose at carbon 6, and fukutin adds the sugar ribitol 5-phosphate to the glycan chain. To assess the roles of POMK and fukutin relative to each other, scientists conducted experiments in which lysates from muscle cells deficient in either POMK or fukutin were incubated with ³²P-labeled ATP or ³H-labeled activated ribitol 5-phosphate. Combined lysates containing both fukutin and POMK were also tested. Dg was then purified and detected by autoradiography and western blot using an antibody against Dg, as shown in Figure 2.
Figure 2 Autoradiograms and western blots of Dg purified from lysates incubated with ³²P-labeled ATP or ³H-labeled ribitol 5-phosphate
Adapted from Kanagawa M, Kobayashi K, Tajiri M, et al. Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy. Cell Rep. 2016;14(9) :2209-23.
-POMT can use activated D-mannose, but not D-glucose, as a substrate. D-glucose and D-mannose are:

Question

Passage
Dystroglycan (Dg) is a transmembrane protein that mediates interactions between the cytoskeleton and the extracellular matrix (ECM) . It binds the ECM protein laminin in an interaction that is required for intercellular communication and muscle membrane structural stability. The Dg-laminin interaction is facilitated by a long carbohydrate chain called an O-mannosyl glycan, which is covalently linked to Dg (Figure 1) .

Figure 1 Schematic of interaction between Dg and laminin, mediated by the Dg-linked O-mannosyl glycanThe O-mannosyl glycan is added to Dg by a series of enzymes called glycosyltransferases. The first enzyme in this series, protein O-mannosyltransferase (POMT) , attaches D-mannose to the hydroxyl groups of serine and threonine residues in an α-linkage through the anomeric carbon. The next sugar in the chain then forms a β-1,4 linkage to the mannose residue, followed by several more steps to produce the full glycan. Genetic inactivation of any of the enzymes in the pathway results in an incomplete glycan and failure to bind laminin, and is the underlying cause of several severe forms of muscular dystrophy known as dystroglycanopathies.Researchers investigating dystroglycanopathies recently discovered the functions of two enzymes in the pathway: protein O-mannose kinase (POMK) and fukutin. POMK phosphorylates Dg-linked mannose at carbon 6, and fukutin adds the sugar ribitol 5-phosphate to the glycan chain. To assess the roles of POMK and fukutin relative to each other, scientists conducted experiments in which lysates from muscle cells deficient in either POMK or fukutin were incubated with ³²P-labeled ATP or ³H-labeled activated ribitol 5-phosphate. Combined lysates containing both fukutin and POMK were also tested. Dg was then purified and detected by autoradiography and western blot using an antibody against Dg, as shown in Figure 2.

Figure 2 Autoradiograms and western blots of Dg purified from lysates incubated with ³²P-labeled ATP or ³H-labeled ribitol 5-phosphate
Adapted from Kanagawa M, Kobayashi K, Tajiri M, et al. Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy. Cell Rep. 2016;14(9) :2209-23.
-POMT can use activated D-mannose, but not D-glucose, as a substrate. D-glucose and D-mannose are:

Quizplus · Accepted Answer

11ecba2d_0e0e_d412_a3bf_81f924b0065d_MD0008_00 Molecules with the same molecular formula but different arrangements of the atoms are called isomers. Stereoisomers are molecules with the same kinds of bonds at any given position but with the bonds oriented differently in space. Stereoisomers have one or more stereocenters, also called chiral centers, which are atoms bonded to four different chemical groups. Molecules that have multiple stereocenters but differ at only one of them are called epimers. D-mannose and D-glucose each have several stereocenters but differ from each other only at the carbon 2 center; therefore, they are called C-2 epimers. Because POMT can use activated D-mannose but not D-glucose as a substrate, it must be able to distinguish between these epimers. (Choice A) Unlike stereoisomers, constitutional isomers have the same molecular formula but different bond types in at least one position (ie, different connectivity between atoms). For example, D-glucose and D-fructose are constitutional isomers, having a carbon with two bonds to oxygen at carbon 1 and carbon 2, respectively. (Choice B) Enantiomers are stereoisomers that differ at every stereocenter, not just one. The enantiomer of D-mannose is L-mannose. (Choice D) Anomers are a special kind of epimer that differ at the anomeric carbon and are designated as the α- and β-forms of the same sugar. This difference can only occur in the cyclical form of the carbohydrate because the anomeric carbon is not a stereocenter in the linear form. Educational objective: Stereoisomers are molecules that differ from each other in the spatial orientation of their bonds at one or more stereocenters (atoms that are bonded to four different chemical groups). Stereoisomers that differ at only one of several centers are epimers whereas those that differ at all centers are enantiomers. Constitutional isomers have the same molecular formula but distinct bond arrangements.

Passage Dystroglycan (Dg) Is a Transmembrane Protein That Mediates Interactions Between