蛋白质水解
蛋氨酸亚砜还原酶
蛋白质周转
生物化学
蛋白质降解
细胞生物学
蛋白酶体
磷酸化
果糖胺
化学
生物
蛋氨酸亚砜
酶
蛋氨酸
蛋白质生物合成
氨基酸
内分泌学
胰岛素
作者
Niki Chondrogianni,Isabelle Petropoulos,Stefanie Grimm,Konstantina Georgila,Betül Karademir,Bertrand Friguet,Tilman Grune,Efstathios S. Gonos
标识
DOI:10.1016/j.mam.2012.09.001
摘要
Proteins are continuously affected by various intrinsic and extrinsic factors. Damaged proteins influence several intracellular pathways and result in different disorders and diseases. Aggregation of damaged proteins depends on the balance between their generation and their reversal or elimination by protein repair systems and degradation, respectively. With regard to protein repair, only few repair mechanisms have been evidenced including the reduction of methionine sulfoxide residues by the methionine sulfoxide reductases, the conversion of isoaspartyl residues to L-aspartate by L-isoaspartate methyl transferase and deglycation by phosphorylation of protein-bound fructosamine by fructosamine-3-kinase. Protein degradation is orchestrated by two major proteolytic systems, namely the lysosome and the proteasome. Alteration of the function for both systems has been involved in all aspects of cellular metabolic networks linked to either normal or pathological processes. Given the importance of protein repair and degradation, great effort has recently been made regarding the modulation of these systems in various physiological conditions such as aging, as well as in diseases. Genetic modulation has produced promising results in the area of protein repair enzymes but there are not yet any identified potent inhibitors, and, to our knowledge, only one activating compound has been reported so far. In contrast, different drugs as well as natural compounds that interfere with proteolysis have been identified and/or developed resulting in homeostatic maintenance and/or the delay of disease progression.
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