Glucose selective phosphorylation with

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

Thiabendazole (Mintezol) inhibits fumarate reductase and electron transport-associated phosphorylation in helminths. Interference with ATP generation decreases glucose uptake and affects the energy available for metabolism. Benzimidazole anthelmintics as a class (e.g., thiabendazole, mebendazole, and albendazole), bind selectively to (3-tubulin of nematodes (roundworms), ces-todes (tapeworms), and trematodes (flukes). This inhibits microtubule assembly, which is important in a number of helminth cellular processes, such as mitosis, transport, and motihty. 

Figure 10. Fine structure of liver glycogen as revealed by selective enzymatic gradation (110). O, , and Q represent glucose residues removed by first, second, and third treatment with muscle phosphorylase represents glucose units removed by amylo-(l - 6) glucosi-dase (the numbers beside these units indicate the number of treatment following phosphoryl-ase action).

Figure 25-14 Mechanism of insulin action. Binding of insulin to the extracellular a-subunit of the insulin receptor induces autophosphorylation of the -subunit of the receptor and phosphorylation of selected intracellular proteins, such as She and the IRS family,These latter phosphoproteins interact with other targets, thereby activating phosphorylation cascades, which result in glucose uptake (in adipose tissue and skeletal muscle), glucose metabolism, synthesis (of glycogen, iipid, and proteins), enhanced gene expression, cell growth, and differentiation, p, protein phosphorylation aPKC, atypical protein kinase C, See text for details.

Several 4-thio-D-glucofuranosylamine disaccharide derivatives such as 8 (a p, 1 3) were obtained by direct condensation of 4-thio-D-glucose with an amino-sugar. A review of the application of palladium si-allyl complexes of unsaturated carbohydrates in fuctionalization at the anomeric centre included the use of 7V-nucleophiles to provide unsaturated JV-glycosyl derivatives. Cyclic l,2-iV,0-phosphate derivatives of aldoses feature as intermediates in selective 2-0-phosphorylation reactions (see Chapter 7). 

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