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I'm trying to find out how many molecules of nucleoside triphosphates (ATP, GTP, UTP and/or CTP) it takes to release enough energy to link two amino acid monomers together with a peptide bond, specifically during the process of mRNA translation.

I've tried to do some research online, but I could not find a reputable source that will say definitely how much energy is consumed in the process. The best answer I could find is formulated based on 'Molecular Biology of the Cell' 4th edition by Alberts B, Johnson A, Lewis J, et al., which is that at least one molecule of ATP is consumed for every peptide linkage. Is this correct?

I've also read on a science forum that the amount of ATP consumed during translation is different for every amino acid, but I could not find a reliable source to back up that claim. Is this true?

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  • $\begingroup$ You might want to think a bit about the boundary of your question, which parts of the whole process do you want to include. Loading the tRNA uses ATP as well, do you want to include other aspects or just the peptide bond formation? I'm not sure if there's a single value here, as far as I remember there are also elongation factors and other proteins that require ATP/GTP for protein biosynthesis. $\endgroup$
    – Mad Scientist
    Nov 24 '15 at 22:46
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    $\begingroup$ I'd agree with the explanation from Alberts et al from Molecular Biology of the Cell - it may see like a lot, but protein synthesis requires a TON of energy. $\endgroup$
    – Vance L Albaugh
    Nov 24 '15 at 23:51
  • $\begingroup$ Duplicate of biology.stackexchange.com/questions/34783/… $\endgroup$
    – WYSIWYG
    Nov 25 '15 at 5:12
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    $\begingroup$ This is an old question, but as it has surfaced again I have cleaned up the title so it reflects the question better. $\endgroup$
    – David
    Aug 22 '17 at 22:29
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Although the question shows considerable effort to achieve clarity, the way it is phrased as:

How many molecules of nucleoside triphosphate… [does] it take to release enough energy

still allows ambiguity, as I would not really regard the NTPs involved in protein synthesis “releasing energy”. So let us consider two reformulations of the question, as the explanation of the answers is of more scientific interest than the actual answers.

1. How many molecules of NTP are hydrolysed in the reactions causing the formation of one peptide bond on the ribosome?

Answer = 3

Formation of each peptide bond involves a cycle consisting of the introduction of a single new aminoacyl-tRNA to the A site of a ribosome carrying a growing polypeptide chain (or initiator tRNA for the first peptide bond), the peptidyl transferase reaction, and than translocation of the extended peptidyl-tRNA from A- to P-site. (See, e.g. Berg et al. online — Ch. 29)

1 ATP is hydrolysed in the aminoacylation reaction:

                Amino Acid + tRNA + ATP → Aminoacyl-tRNA + AMP + PPi

1 GTP is hydrolysed in the aatRNA binding reaction catalysed by EF-Tu/EF1.

1 GTP is hydrolysed in the translocation reaction catalysed by EF-G/EF2

No NTP is consumed directly in the peptidyl transferase reaction — the energy for bond formation comes from the ‘activated’ aminoacyl-tRNA.

Elongation and GTP hydrolysis

2. What is the total energetic cost in molecules of ATP for the formation of one peptide bond?

Here one might argue that:

Answer = 4+

The additional ATP occurs if one considers the total energetic cost of the aminoacylation reaction as 2 ATP, not 1 ATP. This arises from the fact that the ATP is hydrolysed to AMP (+PPi) and not ADP. Recycling of the AMP involves first the use of 1 molecule of ATP in the adenylate kinase reaction to produce ADP:

                                 ATP + AMP ⇄ 2ADP

followed by the energy (from membrane ATP synthase) to regenerate ATP from ADP:

                                 ADP + Pi ⇾ ATP

Why 4+? Certain amino acids (e.g. val and ile) are sufficiently similar to one another that the aminoacyl-tRNA synthetases have evolved a proof reading capacity, in which any incorrectly aminoacylated tRNA is hydrolysed. This only occurs for certain amino acids and at a rate that is difficult to determine, so the wastage of the ATP in this manner cannot be calculated precisely.

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First, during the initiation of translation, a small ribosomal subunit binds to a molecule of mRNA. In a bacterial cell, the mRNA binding site on this subunit recognizes a specific nucleotide sequence on the mRNA just upstream of the start codon. An initiator tRNA, with the anticodon UAC, base-pairs with the start codon, AUG. This tRNA carries the amino acid methionine. And then, this process need one molecular GTP, and GTP--->GDP+Pi, which can provide energy for the assembly. You can find more details in the book Campbell Biology, by Reece, Urry, et.al..

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About 5 ATP molecules are required for the addition of a single amino aid to a growing peptide chain.

I found this answer in Ribosome and transcript copy numbers, polysome occupancy and enzyme dynamics in Arabidopsis by Piques et al.:

The addition of an amino acid to a growing peptide chain requires two ATP molecules for amino acid activation and another two ATP for peptide bond formation and ribosome translation, plus additional costs of about another ATP, for error correction and the synthesis of sequences that are removed during protein maturation.

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  • $\begingroup$ This is plain wrong and phrased in meaningless terms, e.g. "peptide bond formation and ribosome translation". See the chapter on protein biosynthesis in any standard biochemistry text in the last 20 years. $\endgroup$
    – David
    Aug 22 '17 at 22:32
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Actually it depends on the question. Whether you mean to say: How many amino acids are required? Or proteins? There is a characteristic difference between amino acids and proteins. Hence the number. Of amino acids can be determined by the following- If we consider a protein composed of "n" number of amino acids, it takes (4n)-1 number of ATP for the translation process.

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    $\begingroup$ You might want to add some reference to your answer. Just a simple answer without any citations wouldn't work. $\endgroup$
    – another 'Homo sapien'
    Sep 13 '16 at 6:07
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4 ATP : 2 for activation amino acids to bind with specific tRNA. 1 for initiation 1 for elongation to push tRNA to the p site of ribosome

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  • $\begingroup$ Please give some references and add some details for each step. A figure could really help clarify your answer. $\endgroup$
    – Flo
    Aug 23 '17 at 9:24

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