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Post-translational modification

Post-translational modification (PTM) refers to enzymatic modification of proteins following protein biosynthesis. 

 

 

Proteins are synthesized by ribosomes which translating mRNA into polypeptide chains.

 

 

Polypeptide chains may then undergo PTM to form the mature protein product. 

 

 

PTMs are important components in cell signaling.

 

 

PTMs signal prohormones conversion to hormones.

 

 

Post-translational modification of insulin turns it into mature insulin.

 

 

PTMs  can occur on the amino acid side chains or at the protein’s C- or N- termini.

 

 

PTMs can extend the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphate. 

 

 

Phosphorylation is a very common mechanism for regulating the activity of enzymes.

 

 

Phosphorylation is the most common post-translational modification.

 

 

Post-translational modification glycosylation,  the attaching of carbohydrate molecules to proteins 

 

occurs in  eukaryotic and prokaryotic cells.

 

 

Glycosylation can promote protein folding and improve stability as well as serving regulatory functions. 

 

 

PTM  attachment of lipid molecules, lipidation, often targets a protein or part of a protein attached to the cell membrane.

 

 

Other forms of post-translational modification consist of cleaving peptide bonds, and formation  of disulfide bonds.

 

 

Oxidative stress can cause post-translational modifications.

 

 

Amino acid modifications can be used as biomarkers indicating oxidative damage.

 

 

Post-translational modification sites are those that have a functional group that can serve as a nucleophile in the reaction.

 

 

Post-translational modification of proteins can be detected by: mass spectrometry, Eastern blotting, and Western blotting techniques.

 

 

The 10 most common found modifications were as follows:

 

 

Phosphorylation

 

 

Acetylation

 

 

N-linked glycosylation

 

 

Amidation

 

 

Hydroxylation

 

 

Methylation

 

 

O-linked glycosylation

 

 

Ubiquitylation

 

 

Pyrrolidone carboxylic acid

 

 

Sulfation

 

 

Post-translational modifications of epigenetic alterations of histone proteins in specific regions of the brain are  crucial to the molecular basis of addictions.

 

 

The addictive phenotype can be lifelong, with drug craving and relapse occurring even after decades of abstinence.

 

 

In the nucleus accumbens of the brain, Delta FosB functions as a sustained molecular switch and master control protein promoting the development of an addiction.

 

 

Increased dopamine release is recognized as an important factor for addiction.

 

 

About 7% of the US population is addicted to alcohol.

 

 

The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol.

 

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