Home | | Biochemistry | Amino Acid Activation

Chapter: Biochemistry: Protein Synthesis: Translation of the Genetic Message

Amino Acid Activation

What is the “second genetic code”?

Amino Acid Activation

The activation of the amino acid and the formation of the aminoacyl-tRNA take place in two separate steps, both of which are catalyzed by the aminoacyl-tRNA synthetase (Figure 12.6). First, the amino acid forms a covalent bond to an adenine nucleotide, producing an aminoacyl-AMP. The free energy of hydrolysis of ATP provides energy for bond formation. The aminoacyl moiety is then transferred to tRNA, forming an aminoacyl-tRNA.


Aminoacyl-AMP is a mixed anhydride of a carboxylic acid and a phosphoric acid. Because anhydrides are reactive compounds, the free-energy change for the hydrolysis of aminoacyl-AMP favors the second step of the overall reaction. Another point that favors the process is the energy released when pyrophosphate (PPi) is hydrolyzed to orthophosphate (Pi) to replenish the phosphate pool in the cell.



In the second part of the reaction, an ester linkage is formed between the amino acid and either the 3'-hydroxyl or the 2'-hydroxyl of the ribose at the 3' end of the tRNA. There are two classes of aminoacyl-tRNA synthetases. Class I loads the amino acid onto the 2' hydroxyl. Class II uses the 3' hydroxyl. These two classes of enzyme appear to be unrelated and indicate a convergent evolu-tion. Several tRNAs can exist for each amino acid, but a given tRNA does not bond to more than one amino acid. The synthetase enzyme requires Mg2+ and is highly specific both for the amino acid and for the tRNA. A separate synthetase exists for each amino acid, and this synthetase functions for all the different tRNA molecules for that amino acid. The specificity of the enzyme contributes to the accuracy of the translation process. The synthe-tase assures that the right amino acid pairs up with the right tRNA, and this is its primary function. The synthetase has another level of activity as well. An extra level of proofreading by the synthetase is part of what is sometimes called the “second genetic code.”

What is the “second genetic code”?

The two-stage reaction allows for selectivity to operate at two levels: that of the amino acid and that of the tRNA. The specificity of the first stage uses the fact that the aminoacyl-AMP remains bound to the enzyme. For example, isoleucyl-tRNA synthetase can form an aminoacyl-AMP of isoleucine or the structurally similar valine. If the valyl moiety is then transferred to the tRNA for isoleucine, it is detected by an editing site in the tRNA synthetase, which then hydrolyzes the incorrectly acylated aminoacyl-tRNA. The selectivity resides in the tRNA, not in the amino acid.

The second aspect of selectivity depends on the selective recognition of tRNAs by aminoacyl-tRNA synthetases. Specific binding sites on tRNA are rec-ognized by aminoacyl-tRNA synthetases. The exact position of the recognition site varies with different synthetases, and this feature, in and of itself, is a source of greater specificity. Contrary to what one might expect, the anticodon is not always the part of the tRNA that is recognized by the aminoacyl-tRNA synthe-tase, although it frequently is involved. Figure 12.7 shows the locations of the recognition sites for the tRNAs for various amino acids.


The recognition of the correct tRNA by the synthetase is vital to the fidelity of translation because most of the final proofreading occurs at this step.

Summary

Before amino acids can be incorporated into a peptide, they must be activated.

Amino acids are activated through a reaction with ATP yielding an amino acid bonded to AMP. The AMP-bound amino acid is then reacted with a tRNA to yield an amino acyl tRNA.

The enzymes responsible for activation are called aminoacyl-tRNA synthetases.


Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Biochemistry: Protein Synthesis: Translation of the Genetic Message : Amino Acid Activation |


Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.