Amyloid aggregates are deposited as stable, insoluble fibrils in the extracellular tissues of organs such as the brain, eye or liver. Consequentially, the functions of these organs are disturbed, causing diseases ranging from Alzheimer's to Creutzfeldt-Jakob disease (the human version of mad cow disease).
The term amyloidosis is used to describe diseases in which proteins that are normally globular and soluble are deposited as stable, insoluble fibrils in the extracellular space of tissues.
The structure of amyloid is nearly indestructable under physiological conditions, most likely due to the large number of difficult-to-break hydrogen bonds. If the amyloid form of a protein is more stable than the native state, then
The relative stability of the amyloid structure makes consideration of these questions important. Try to formulate reasons for this phenomena, then click here to find out some hypothesized answers to these questions.
Several answers to the quandry of amyloids have been proposed:
- The cellular environment is probably key in this process: if the environment is such that denaturation can occur where unfolded chains tend to aggregate, amyloid disease is likely to occur.
- Cooperativity of the protein-folding process is another piece to the puzzle. Protein folding is usually observed in a 'two state' process: folded & denatured. Any partially unfolded states must be small in number and brief in existence, and folded states must be firmly locked in their respective conformations. The diverse functions of proteins has long been attributed to this cooperativity, and it now appears that resistance to amyloid formation could be similarly attributed.
- Conditions such as low pH and reducing environments may advocate the formation of amyloid by providing conditions under which denaturation and reduction of disulfide bonds, respectively, may occur. These changes may give rise to intermediates that are an indication of the loss of the cooperativity associated with the wild-type protein.
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