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World J Gastroenterol. Aug 7, 2022; 28(29): 3780-3792
Published online Aug 7, 2022. doi: 10.3748/wjg.v28.i29.3780
Structural changes of proteins in liver cirrhosis and consequential changes in their function
Nikola Gligorijević, Simeon Minić, Olgica Nedić
Nikola Gligorijević, Olgica Nedić, Department of Metabolism, University of Belgrade-Institute for the Application of Nuclear Energy, Belgrade 11080, Serbia
Simeon Minić, Centre of Excellence for Molecular Food Sciences and Department of Biochemistry, University of Belgrade-Faculty of Chemistry, Belgrade 11000, Serbia
Author contributions: Gligorijevic N performed the literature search, writing and prepared the figure; Minic S performed the literature search and writing; Nedic O designed the outline, performed the literature search and coordinated the writing of the paper.
Supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, No. 451-03-9/2021-14/200019.
Conflict-of-interest statement: All authors report no relevant conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nikola Gligorijević, PhD, Research Associate, Department of Metabolism, University of Belgrade-Institute for the Application of Nuclear Energy, Banatska 31b, Belgrade 11080, Serbia. nikolag@inep.co.rs
Received: January 13, 2022
Peer-review started: January 13, 2022
First decision: May 29, 2022
Revised: May 30, 2022
Accepted: June 30, 2022
Article in press: June 30, 2022
Published online: August 7, 2022
Abstract

The liver is the site of synthesis of the majority of circulating proteins. Besides initial polypeptide synthesis, sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose. Posttranslational modifications (PTMs) design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose. PTMs can change under pathological conditions, giving rise to aberrant or overmodified proteins. Undesired changes in the structure of proteins most often accompany undesired changes in their function, such as reduced activity or the appearance of new effects. Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control. Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation, nitration, glycosylation, acetylation, and ubiquitination. Some of them predominantly affect proteins that remain in liver cells, whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation. Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases, including cirrhosis. This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

Keywords: Liver cirrhosis, Post-translational modifications, Circulation, Protein function, Protein structure, Chronic liver disease

Core Tip: Chronic liver diseases and cirrhosis are accompanied by various metabolic disorders, some of which affect proteins. Besides changes in the concentration, structural alterations of proteins occur, mostly at the level of posttranslational modifications (PTMs). Five frequent cirrhosis-related PTMs are oxidation, nitration, glycosylation, acetylation, and ubiquitination. Some are more specific for the circulating proteins, whereas others are more specific for liver tissue-residing proteins. PTMs influence folding, stability, half-life, aggregation, and function of proteins. Modified proteins with altered function contribute to further progression of liver pathology. An overview of cirrhosis-related alterations of PTMs of specific proteins is the topic of this article.