A model for glycine self-assembly in yeast

Inborn errors of metabolism are single gene disorders resulting from defects in biochemical pathways. Although these disorders are individually rare, collectively they amount up to a substantial portion of childhood disability and deaths. Lately, there have been numerous advances in terms of awareness and knowledge regarding these conditions, but unfortunately their mechanisms are not fully understood. The inborn error of metabolism disorder Non Ketotic Hyperglycinemia (NKH) affects mainly newborns and infants. The disorder is lethal in many of the cases or otherwise can cause severe damage to the nervous system, impeding normal motor and intellectual development. An extension of the amyloid hypothesis of protein accumulation and amyloid formation has been recently shown in our lab to include also certain metabolites such as amino acids and nucleobases. In this study, we established an in vivo yeast model system for the study of NKH whereby addition of glycine to the growth medium resulted in dose-dependent growth inhibition. In addition, upon glycine feeding we could detect a fluorescent signal using the amyloid dye ProteoStat, which is known to effectively detect the presence of intracellular amyloid-like deposits. Furthermore, using electron microscopy, a fibrillary morphology of glycine assemblies could be observed. This model opens up exciting prospects for understanding the mechanism of the disease and for drug screening in order to identify potential treatment.