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The role of protein aggregation in



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E learning in pharmaceutical continuing

The role of protein aggregation in 
programmed erythrocyte death 
Aggregation of membrane proteins probably affects the activity 
of certain enzymes or transport proteins which are important 
as energy providers, for instance aggregation of band 3 protein 
(AE1) in aging erythrocytes. It is the most abundant protein of the 
erythrocyte membrane (almost one million protein molecules in 
a single red blood cell), accounting for 25% of integral membrane 
proteins and occupying 10% of red blood cell surface area. This 
protein, similar to the membrane potential, is regarded as the 
main factor determining the shape attained by the erythrocyte. 
Band 3 protein conformational changes induce the outlow of 
ions and the inlow of anions across the membrane. Its inactiva
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tion as a result of aggregation leads to failure to maintain ionic 
equilibrium in the cell. 
The conformational changes of the band 3 protein and related 
probable enzymatic processing result in decreased activity of 
certain glycolytic enzymes which bind to the protein intracel-
lular fragment. This process inactivates the following glycolytic 
enzymes: phosphofructokinase, 3-phosphoglycerol aldehyde 
dehydrogenase and aldolase. Regulation of complex formation 
involves also phosphorylation and dephosphorylation of band 3 
protein N-terminus with the process being dependent on eryth-
rocyte oxidoreduction potential [11, 32, 33].
Apart from loss of certain proteins that are important for 
maintaining erythrocyte function, the decrease in cell surface 
leads also to changes in its shape and spatial arrangement of 
cytoskeletal proteins (they are attached to band 3 protein).
Impairment of any element in internally coupled metabolic 
reactions results in deregulation which may independently lead 
to death. It has been proved in blood diseases which shorten 
blood cell life span. They arise from defects in metabolic path
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System biolog
y
28
The criteria of life and aging from a molecular viewpoint…
ways (hemolytic anemia due to deiciency or reduced activity of 
glycolytic enzymes, defects of the pentose phosphate pathway, 
and anemia resulting from alterations in the cytoskeleton and 
defects in integral membrane proteins).

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