Draw the mechanism for the two steps reaction catalyzed by aminoacyl-tRNA synthetases that gives rise to...

Draw the mechanism for the two steps reaction catalyzed by aminoacyl-tRNA synthetases that gives rise to "activated" tRNA

Expert Solution

The activation reaction is catalyzed by specific aminoacyl-tRNA synthetases, which are also called activating enzymes. The first step is the formation of an aminoacyl adenylate from an amino acid and ATP. This activated species is a mixed anhydride in which the carboxyl group of the amino acid is linked to the phosphoryl group of AMP; hence, it is also known as aminoacyl-AMP.

The next step is the transfer of the aminoacyl group of aminoacyl-AMP to a particular tRNA molecule to form aminoacyl-tRNA.

The sum of these activation and transfer steps is

The ΔG°′ of this reaction is close to 0, because the free energy of hydrolysis of the ester bond of aminoacyl-tRNA is similar to that for the hydrolysis of ATP to AMP and PPi. As we have seen many times, the reaction is driven by the hydrolysis of pyrophosphate. The sum of these three reactions is highly exergonic:

Thus, the equivalent of two molecules of ATP are consumed in the synthesis of each aminoacyl-tRNA. One of them is consumed in forming the ester linkage of aminoacyl-tRNA, whereas the other is consumed in driving the reaction forward.

The activation and transfer steps for a particular amino acid are catalyzed by the same aminoacyl-tRNA synthetase. Indeed, the aminoacyl-AMP intermediate does not dissociate from the synthetase. Rather, it is tightly bound to the active site of the enzyme by noncovalent interactions. Aminoacyl-AMP is normally a transient intermediate in the synthesis of aminoacyl-tRNA, but it is relatively stable and readily isolated if tRNA is absent from the reaction mixture.

We have already encountered an acyl adenylate intermediate in fatty acid activation. The major difference between these reactions is that the acceptor of the acyl group is CoA in fatty acid activation and tRNA in amino acid activation. The energetics of these biosyntheses are very similar: both are made irreversible by the hydrolysis of pyrophosphate.

queen_honey_blossom answered 2 years ago

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