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Amyloid fibrils are elongated nanoscale structures that bind to specific dyes (including thioflavin T and Congo red). Amyloid fibrillar assemblies or their early intermediates are known to induce apoptotic cytotoxic effect. Until recently, amyloid fiber formation was observed only with proteins and peptides. We reported in 2012 that a single amino acid, phenylalanine, could also form typical amyloid fibrils with the same morphology, dye\u2010binding specificity, and electron diffraction pattern as protein amyloids. X\u2010ray crystallography demonstrated the formation of supramolecular \u03b2\u2010sheet\u2010like organization by phenylalanine at its zwitterionic form. Metabolite amyloids had pronounced cytotoxicity that could be depleted by treatment with antibodies raised against the phenylalanine structures. We suggested that the observed amyloid formation could explain some of the symptoms observed in phenylketonuria (PKU) upon the accumulation of phenylalanine. Follow\u2010up studies by other groups revealed the ability of phenylalanine amyloids to bind to membranes, as observed with protein amyloids. Furthermore, the doxycycline amyloid formation inhibitor was shown to also affect the formation of phenylalanine amyloids. In 2015, it was reported that other metabolites involved in metabolic disorders, including adenine, uracil, tyrosine, and orotic acid, could form amyloid\u2010like assemblies. It was further demonstrated that the assemblies induce apoptotic cell death. Taken together, we suggest a new hypothesis to understand the etiology of degenerative processes observed in inborn error of metabolism disorders and indicate new avenues for treatment.<\/jats:p>","DOI":"10.1007\/s10545-016-9946-9","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T12:06:21Z","timestamp":1465214781000},"page":"483-488","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Metabolite amyloids: a new paradigm for inborn error of metabolism disorders"],"prefix":"10.1002","volume":"39","author":[{"given":"Ehud","family":"Gazit","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Biotechnology, Department of Materials Science and Engineering Tel Aviv University Tel Aviv 6997801 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