The pathogenesis of amyloid deposition: a new hypothesis.
Amyloid proteins are probably derived from a variety of precursor glycoproteins. It is postulated that there may be at least two key events in the pathogenesisi of amyloidosis. The first is an increase in the load of glycoprotein being brought to a site of degradation. In the case of myeloma this might be in the form of excess immunoglobulin light chains. In the case of secondary amyloidosis the form taken could be enzyme-alpha-globulin complexes. The second is an inability of the degrading site to handle the arriving substrate at a sufficiently rapid rate, the rate limiting step being at some point along the degradation pathway. We postulate that an acquired enzyme deficiency prevents removal of the carbohydrate moiety of the presented glycoprotein. This results in the accumulation of a normal intermediate (amyloid protein) during the breakdown of the glycoprotein substrate. Evidence for the operation of these mechanisms is discussed and their detailed nature and implications considered.
D000510:Alpha-Globulins; D000682:Amyloid / Q000378:metabolism / Q000502:physiology; D000686:Amyloidosis / Q000209:etiology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000502:physiology
D000510:Alpha-Globulins; D000682:Amyloid; D006023:Glycoproteins