1-Phosphorylation of carbohydrates

Mechanistic features of phosphoryl transfer and methods of investigation. The chemical phosphorylation of carbohydrates is of importance only in the synthesis of phosphorylated carbohydrates of biological importance. Common phosphorylating agents for monophosphates are dibenzyl or diaryl phosphorochloridates, ClPO(OAr)2 and ClPO(OBn)2 benzyl groups can be removed by catalytic hydrogenation. 

CORI, C. F. (1942) Phosphorylation of carbohydrates. In A Symposium on Respiratory Enzymes, p. 175, Univ. of Wisconsin Press, Madison. 

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. 

Generally speaking, the phosphorylated deoxysugars undergo the usual reactions of carbohydrates without complication. For instance, both 2-deoxy D-ribose 5-phosphate (52, 59) and 2-deoxy D-xylose 5-phosphate (2) can be reduced to the corresponding 2-deoxy d-erythro- (48) and 2-deoxy D-threo-pentitol 5-phosphates (49). 2-deoxy ribose 5-phosphate has also been oxidized (52) to the corresponding phosphorylated acid (50). 

Figure 25.7 Glycoprotein formation occurs by initial phosphorylation of the starting carbohydrate to a glycosyl phosphate, followed by reaction with UTP to form a glycosyl uridine 5 -diphosphate. Nucleophilic substitution by an -OH (or -NH2) group on a protein then gives the glycoprotein.

Unfortunately, the phosphorylated form of the starting aldehyde is expensive, and dephosphorylation by a phosphatase requires an additional step. Therefore, the challenge was to obtain a mutant aldolase that not only accepts nonphos-phorylated substrates but also turns over the enantiomeric aldehyde (29) stereoselectively with formation of (30), which is a precursor of carbohydrate (31) (see Scheme 2.8) [74] ... 

Figure 16-2. The citric acid cycle the major catabolic pathway for acetyl-CoA in aerobic organisms. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with HjO, and oxidized to CO2 with the release of reducing equivalents (2H). Subsequent oxidation of 2H in the respiratory chain leads to coupled phosphorylation of ADP to ATP. For one turn of the cycle, 11 are generated via oxidative phosphorylation and one arises at substrate level from the conversion of succinyl-CoA to succinate.

The free energy of the phosphorylated histidine (P His) or cysteine (P Cys) is comparable with the free energy of PEP (AG° = — 61.5 kJ mol ). The reactions (1) to (4) are therefore fully reversible under physiological conditions, whereas reaction (5) is irreversible. The substrate when bound to the domain IIC (or IID) obtains the phosphoryl group from the unit IIB, via unit IIA, which is rephosphorylated by P HPr. Efficient translocation of carbohydrates depends on the phosphorylated IIB domain. The release of the phosphorylated substrate terminates the uptake process. 

ASPECTS OF CARBOHYDRATE OXIDATION, ELECTRON TRANSFER, AND OXIDATIVE PHOSPHORYLATION... 

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