The Role of Lysine Acetylation in Human Disease

Many different factors can contribute to Human health and disease response and regulation. The role of these factors is constantly being researched by scientists to throw light on how they function in a healthy organism.

Much has been learned over the years as ever more powerful methods have been developed in laboratories worldwide. One such area of interest has been in the role of amino acids, a set of functionally important biomolecules, which include lysine.

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Lysine – An Overview

Lysine is a vital amino acid and plays an important part in biological processes in the Human body. A basic, charged (at physiological pH), an aliphatic amino acid containing an α-amino group, α-carboxylic acid group, and a side chain lysyl, it is encoded by the codons AAG and AAA.

Vital to the production of protein molecules in the body, lysine cannot, however, be synthesized in the body. It must be gained from dietary sources and supplements. Lysine is known as an essential amino acid.

It is necessary for tissue repair and growth, and the production of antibodies, hormones, and enzymes. Lysine plays a role in other important biological processes including the cross-linking of collagen polypeptides and the production of carnitine, a key molecule in fatty acid production.

Acetylation

Acetylation is the reaction where an acetyl functional group is introduced into a chemical compound. In the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, it is termed ethanoylation.

Conversely, deacetylation is the removal of an acetyl group. The introduced acetyl group replaces an active hydrogen atom, resulting in an acetoxy group.

There are two translational mechanisms that facilitate acetyl group attachment. These are either co- or post-translational attachment to either the ε-amino group of lysine residues or the α-amino group of the N-terminus of target proteins.

A variety of enzymes catalyze these reactions, including N-terminal and lysine acetyltransferases. In the process of lysine acetylation, an acetyl group is added to the sidechain of a lysine residue.

Current Understanding of the Role in Human Disease

Lysine acetylation plays a role in various pathologies and conditions in the human body. Lysine acetylation of proteins is one of the most common post-translational modifications (PTMs) in organisms. The process regulates thousands of proteins in a diverse range of biological processes.

Curiously, lysine acetylation is enzymatically reversible, regulated by metabolism-dependent mechanisms that are tightly regulated in the body.

This complex interplay between the processes of lysine acetylation and deacetylation is a crucial factor in many different cellular processes. The mechanisms are elusive, but there is much research being carried out into the physiological roles the process plays in human disease.

It is known that lysine acetylation and deacetylation play an important part in gene and protein regulation and that there are consequential effects of perturbations upon the process, whether it be elevated or depressed levels of acetylation or deacetylation.

Recent research suggests that lysine acetylation can play a role in factors such as inflammatory response, cancer, and even addiction, as well as a catalog of other medical conditions.

Cancer

In the case of cancer, several lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) have been linked to the development of the disease. Bromodomains, a family of evolutionarily conserved domains that recognize acetylated lysine residues, have also been implicated.

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Recent research has been carried out into the testing of small molecules which target these proteins as potential therapeutics. The stoichiometry of lysine acetylation in cancer is being explored as a promising field to gain knowledge about the process.

Inflammation

In a 2011 study by Loukia G Tsaprouni et al., the association of lysine acetylation with inflammatory gene regulation (which has implications for the study of inflammatory bowel diseases such as Crohn’s Disease and Ulcerative colitis) was explored.

The team used two animal models to investigate its role. Part of the results pertaining to Chrohn’s disease obtained by the team showed a slight induction of acetylation on H4 in the non-inflamed ileum but a significant elevation in the inflamed tissues.

Clearly, acetylation of lysine plays a major part in the inflammatory response in the condition and the team hoped that the results of this study will aid in the development of therapeutics which target the process.

Addiction

Alterations in gene expression are believed contribute to addiction in the human body, playing a role in the development and maintenance of the addicted state, even when the user has not taken the drug for a long time.

As acetylation is involved in the regulation of chromatin structure, itself a contributing factor to the translation of a variety of environmental stimuli including drugs (for example, cocaine) into gene expression, this has emerged as an area of interest to scientists working in the field of addiction research.

Studies are ongoing into how these drugs alter acetylation in the reward regions of the brain, the enzymes involved in the pathways, and ultimately the role of acetylation in addiction-related behaviors.

In Conclusion

Lysine acetylation is an important biochemical process that has profound but as yet poorly understood effects upon the physiological functions in Humans and other eukaryotic and prokaryotic organisms.

It plays a role in processes such as gene expression, protein regulation, inflammation, cancer, and addiction, amongst other socially and medically important diseases and conditions that are the subject of focus within the scientific community.

Researchers working in this field of the study hope that with a better understanding of this enigmatic biological process novel and improved therapeutics can be developed which will provide benefits for those that are afflicted by them.

Written by

Reginald Davey

Reg Davey is a freelance copywriter and editor based in Nottingham in the United Kingdom. Writing for News Medical represents the coming together of various interests and fields he has been interested and involved in over the years, including Microbiology, Biomedical Sciences, and Environmental Science.