Glucose 6-phosphate mammalian

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. 

A. Inositol Phosphates.—Phosphatidyl inositol (71) is hydrolysed in mammalian tissues to wyo-inositol 1,2-cyclic phosphate (72).i myoinositol 1-phosphate (73) is released simultaneously but is not converted into (72) by the enzyme system. Periodate oxidation of (73) liberates orthophosphate quantitatively, the unstable dialdehyde phosphate (74) being an intermediate. Little or no orthophosphate is released from glucose 6-phosphate under the same oxidative conditions, and this reaction has been used to assay (73). 

The 357-residue mammalian glucose-6-phospha-tase plays an important role in metabolism (Chapter 17). Defects in the enzyme cause a glycogen storage disease (Box 20-D) and severe disruption of metabolism.731 However, the molecular basis of its action is not well-known. Furthermore, the active site of the enzyme is located in the lumen of the endoplasmic reticulum732 and glucose-6-phosphate must pass in through the plasma membrane. An additional glucose-6-phosphate transporter subunit may be required to allow the substrate to leave the cytoplasm.73... 

Agren 112) and Engstrom 113) isolated serine phosphate from mammalian alkaline phosphatase that had been incubated with inorganic phosphate in acid pH (<6). Engstrom 114) and Schwartz and Lipmann 35) later obtained similar results with E. coli alkaline phosphatase. They found that a large percentage of the enzyme is phosphorylated, that compounds like glucose 6-phosphate and sodium arsenate inhibit... 

Because of its roles in the synthesis of glycogen, in isomerization of hexose phosphates, and as a precursor for numerous biosynthetic intermediates, UDP-glucose is regarded as a central hexose derivative in mammalian metabolism. In bacteria and plants, both ADP-glucose (production of storage polysaccharide) and UDP-glucose (sugar interconversions and biosynthesis) play important roles as precursors. 

NADPH is required for many biosynthetic sequences. It is generated in different kinds of cells by a variety of reactions, including an NADP+-linked oxidation of malate to pyruvate and C02 and transfer of hydride ion from NADH to NADP+ in a mitochondrial reaction that is driven by metabolic energy. However, in many cases, including in the mammalian liver, a major part of the NADPH requirement is met by oxidation of glucose-6-phosphate to ribulose-5-phosphate and C02. The four electrons that are released by the oxidation are transferred to two molecules of NADP+. 

For example, sodium ion is the principal cation of the extracellular fluid of the mammalian body, comprising, as the chloride and bicarbonate, more than 90% of the total solute in that fluid. Ingestion of sodium chloride solutions is used to replace salt lost by excessive perspiration. More sophisticated preparations have been proposed for this purpose one such preparation5 comprises mainly sodium chloride, supplemented with smaller amounts of potassium and phosphate ions to approximate the average composition of sweat in a sweetened glucose solution. 

Monosaccharides may possess functionalities other than hydroxyls. Amino sugars are aldoses or ketoses which have a hydroxyl group replaced by an amino functionality. 2-Amino-2-deoxy-glucose is one of the most abundant amino sugars it is a constituent of the polysaccharide chitin. It also appears in mammalian glycoproteins, linking the sugar chain to the protein. Monosaccharides may also be substituted with sulfates and phosphates. Furthermore, deoxy functions can often be present, and important examples of this class of monosaccharides are L-fucose and L-rhamnose. 

Some mammalian cells have the ability to metabolize glucose 6-phosphate in a pathway that involves the production of C3, C4, C5, C6, and C7 sugars. This process also yields the reduced coenzyme, NADPH, which is oxidized in the biosynthesis of fatty acids and steroids (Chap. 13). Consequently, this metabolic pathway is of major importance in those cells involved in fatty acid and steroid production, such as the liver, lactating mammary gland, adrenal cortex, and adipose tissue. The pentose phosphate pathway, which does not require oxygen and which occurs in the cytoplasm of these cells, has two other names the phosphogluconate pathway (after the first product in the pathway) and the hexose monophosphate shunt (since the end products of the pathway can reenter glycolysis). 

UDP-D-xylose, GDP-D-mannose, GDP-L-Fucose, or CMP-D-A-acetylneuraminic acid. Mammalian GTs also use dolichol-diphosphate-GlcNAc2Man9GlC3, dolichol-phosphate-mannose and dolichol-phosphate-glucose (Fig. 2). 

In plants, inositol is biosynthesized from glucose 1-phosphate via inosose 1-phosphate, which is reduced into ID-inositol 3-phosphate (INOl pathway). After dephosphorylation by inositol phosphate monophosphatase, myo-inositol is fed into biosynthesis of inositol phospholipids via a Kennedy-like sequence. In mammalian organisms, inositol is acquired from the diet and is also biosynthesized via INOl. The latter pathway, rather than the inositol phosphate phosphatase, seems to be a more promising target of antipsychotic drugs (17, 18) (see Fig. 2). 

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