Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

Skeletal muscle makes up 30-40% of the total body mass. It is of great significance in maintaining digestion, inhaling and exhaling, sustaining body posture, exercising, protecting joints and many other aspects. Moreover, muscle is also an important metabolic organ that helps to maintain the balance of sugar and fat. Defective skeletal muscle function not only limits the daily activities of the elderly but also increases the risk of disability, hospitalization and death, placing a huge burden on society and the healthcare system. Sarcopenia is a progressive decline in muscle mass, muscle strength and muscle function with age caused by environmental and genetic factors, such as the abnormal regulation of protein post-translational modifications (PTMs).

Wilson’s disease (WD) is an inherited disorder that leads to copper accumulation, but the detailed pathogenic mechanism is uncertain and diagnosis can be difficult without genetic testing because of similarities to other more common diseases.To investigate the metabolomic features of WD, and elucidate its difference with other normal copper metabolism disease.We performed targeted and untargeted metabolomic profiling using ultra-high performance liquid chromatography-tandemmassspectrometry (UPLC-MS/MS) and liquid chromatography-tandemmassspectrometry (LC-MS).We compared the metabolomic profiles of two subgroups of WD patients, hepatic WD(H-WD)and neurological WD (N-WD); of H-WD patients and liver cirrhosis patients (who have similar symptoms, but normal copper levels);and of N-WD patients and Parkinson’s disease patients (who have similar symptoms, but normal copper levels). Pairwise comparisons indicated distinctive metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson’s disease patients, and H-WD and liver cirrhosis patients. We then used logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that distinguish H-WD from liver cirrhosis, and N-WD from Parkinson’s disease. Based on the spatial distribution of the data obtained by PLS-DA analysis, we found that there are different hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(16:0_16:1_22:6), TG(16:0_16:0_22:6) and TG(16:0_16:1_22:5)) between H-WD and N-WD. Furthermore, WD patients have metabolic characteristics that distinguish it from other analogous diseases (liver cirrhosis and Parkinson's disease). Through analysis, WD showed significant differences in the levels of metabolites in some critical metabolism pathways and in the levels of many lipids. ROC analysis indicated that 3 metabolites may be considered as candidate biomarkers for diagnosing WD.

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