Desferrioxamine synthesis

Deoxyepinephrine, chemiluminescence, 647 Deoxygenation, hydroperoxides, 153 DEPT (distortionless enhancement by polarization transfer), 725 -6 6,9-Desdimethylartemisinin, synthesis, 288 Desferrioxamine, PfATP6 enzyme inhibition, 1313... 

The uptake of iron from transferrin into cells has been best studied for reticulocytes, where there is heavy demand for iron for the synthesis of heme. Reticulocytes and, by analogy, other mammalian cells have receptor molecules on their plasma surface which bind transferrin. Characterization of the transferrin receptor from rabbit reticulocytes suggests that it is probably a glycoprotein of molecular weight around 200 000. The number of receptor sites in cells varies in response to the conditions. For example, treatment of K562 cells with the efficient iron chelator desferrioxamine results in an increase in the total number of receptors for transferrin.1142... 

The use of chelating or complexing agents to treat metabolic dysfunction. The classical example is the use of D-penicillamine to treat Wilson s disease, which is caused by an inability of the body to metabolize copper in the normal way. Another example is the use of desferrioxamine for iron overload in Cooley s anemia, which is caused by a fault in hemoglobin synthesis. 

The high affinity for oxidized iron makes the siderophores ideal candidates for chelation therapy where the body is becoming overwhelmed by iron(III) either through acute poisoning or conditions like haemochromatosis that can occur when patients receive frequent blood transfusions. While enterobactin would seem to be the primary choice it has two major drawbacks its synthesis is complicated and, although both isomers bind iron(III) to the same extent, only the L-isomer has activity in vivo. Consequently desferrioxamine B is the agent of choice. 

Dihydropteridine reductase is an important enzyme in the synthesis of several important neurotransmitters, such as tyrosine and acetyl choline. They found that erythrocyte levels of dihydropteridine reductase activity were less than predicted values, and correlated with plasma aluminum levels (Altmann et ah, 1987). After treatment with desferrioxamine, red cell dihydropteridine reductase activity levels doubled. Although brain levels of dihydropteridine reductase activity were not evaluated, it was suggested that high brain aluminum levels might lead to decreased availability of dihydropteridine reductase in the brain. It has been suggested that the mere presence of an increased body aluminum burden has an adverse effect on overall mortality (Chazan et al, 1988). More specifically, an increased body aluminum burden (estimated by the desferrioxamine infusion test) has been associated with memory impairment and increased severity of myoclonus with decreased motor strength (Sprague et al., 1988). 

Hider RC, Porter JB, Singh S (1994) The design of therapeutically useful iron chelators. In Bergeron RJ, Brittenham GM (eds) The development of iron chelators for clinical use. CRC Press, Boca Raton, pp 353-371 Hoffbrand AV, Ganeshaguru K, Hooton JWL, Tattersall MHN (1976) Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells. Br J Haematol 33 517-526... 

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