Acetylation is a fundamental and widespread biological process. This biochemical modification involves adding a small chemical group to various molecules within cells. It acts as a molecular switch, influencing numerous cellular activities and pathways, and is essential for maintaining proper cellular function.
Understanding the Basic Chemistry
At its core, acetylation is a chemical reaction that introduces an acetyl group into a molecule. The acetyl group is a distinct chemical unit composed of two carbon atoms, three hydrogen atoms, and one oxygen atom, represented by the formula -COCH₃. This group is derived from acetic acid and contains a methyl group single-bonded to a carbonyl group.
The transfer of this acetyl group occurs from a donor molecule known as acetyl-coenzyme A (acetyl-CoA). Acetyl-CoA is a central metabolic intermediate, linking various metabolic pathways and serving as the primary source of acetyl units for these reactions. The process involves the addition of the acetyl group to specific amino acid residues, primarily lysine residues, within a protein.
When an acetyl group is added to a lysine residue, it neutralizes the positive charge present on that lysine. This change in charge can alter the protein’s overall charge and shape, which in turn impacts its interactions with other molecules. The reaction is catalyzed by enzymes known as acetyltransferases.
Key Biological Targets and Processes
Acetylation occurs broadly within cells, modifying a diverse array of molecules. Thousands of different proteins are identified as being acetylated in mammalian cells. These modifications can happen both during protein synthesis and after the protein has been formed.
Histones are a prominent example of proteins that undergo acetylation. These proteins are responsible for packaging long strands of DNA into a compact structure called chromatin within the cell nucleus. Acetylation of histones primarily occurs on lysine residues located in their N-terminal tails, which protrude from the nucleosome core.
Beyond histones, non-histone proteins are also subject to acetylation. These include enzymes involved in metabolism, transcription factors that regulate gene activity, and structural proteins that maintain cell shape. N-terminal acetylation, which modifies the very beginning of a protein, affects a large percentage of human proteins.
How Acetylation Influences Cellular Function
The addition of an acetyl group to a molecule has diverse and significant effects on cellular function. For histones, acetylation directly influences the structure of chromatin. By neutralizing the positive charge on histones, acetylation weakens their interaction with the negatively charged DNA.
This reduced interaction leads to a more relaxed or “open” chromatin structure. In this relaxed state, the DNA becomes more accessible to the cellular machinery responsible for gene transcription, promoting gene expression. Conversely, when acetyl groups are removed, chromatin condenses, making DNA less accessible and repressing gene activity.
For non-histone proteins, acetylation can alter their stability, enzyme activity, and interactions with other proteins. Acetylation can either stabilize or destabilize proteins, influencing their lifespan within the cell. It can also modulate the activity of enzymes by changing their shape or the accessibility of their active sites. Furthermore, acetylation can affect where a protein is located within the cell and its ability to bind to other proteins, which is important for cellular signaling pathways.
Reversibility and Regulation
Acetylation is a dynamic and reversible process, meaning acetyl groups can be added and removed as needed. This reversibility allows cells to control protein function and cellular processes in response to changing conditions. The balance between adding and removing acetyl groups is maintained by two main classes of enzymes.
Enzymes called acetyltransferases (also known as lysine acetyltransferases or KATs, and histone acetyltransferases or HATs) are responsible for adding acetyl groups to molecules. These enzymes transfer the acetyl group from acetyl-CoA to their target proteins. HATs regulate gene expression by acetylating histones, leading to an open chromatin structure.
Conversely, enzymes called deacetylases (also known as lysine deacetylases or KDACs, and histone deacetylases or HDACs) remove acetyl groups. HDACs reverse the action of HATs, leading to a more condensed chromatin structure and gene repression. The coordinated action and balance between these acetylating and deacetylating enzymes maintain cellular homeostasis.