Question

The price of protein synthesis. What is the smallest number of molecules of ATP and GTP consumed in the synthesis of a 200 -residue protein, starting from amino acids? Assume that the hydrolysis of \(\mathrm{PP}_{1}\) is equivalent to the hydrolysis of ATP for this calculation.

Short answer

200 ATP and 401 GTP are consumed.

Step-by-step solution

Understanding Protein Synthesis Requirements

Protein synthesis relies on the sequential addition of amino acids according to the mRNA template. Each amino acid added to the growing polypeptide chain requires a series of steps that consume ATP and GTP molecules.

ATP Consumption for Amino Acid Activation

Each amino acid must be activated by its corresponding aminoacyl-tRNA synthetase, which requires the hydrolysis of one molecule of ATP to AMP and PPi. Since we have 200 amino acids, the total ATP consumption for activation is \(200\text{ ATP} \times 1\text{ per amino acid} = 200\text{ ATP}\).

GTP Consumption for Translation

During translation, two GTP molecules are used for each peptide bond formation during elongation: one for the formation of the peptide bond and another for the translocation of the ribosome. Thus, the total GTP consumption for 200 residues is \(200 \times 2 = 400\text{ GTP}\).

Accounting for Additional Steps in Protein Synthesis

Initiation of translation requires an additional GTP for the initiation complex assembly but doesn't need another ATP or GTP directly related beyond this additional initiation step.

Total Energy Consumption

Summing up all parts, the smallest number of ATP molecules is 200 (consumed in amino acid activation), and the smallest number of GTP molecules is 401 (400 for elongation and 1 for initiation).

Key concepts

ATP Consumption

In the process of protein synthesis, ATP plays a crucial role, especially during the initial phase known as amino acid activation. Our cells cannot just randomly combine amino acids; they require a step-by-step energy-driven process to ensure accuracy.
Here's how ATP is consumed in this context:

• **Amino Acid Activation**: Each of the 200 amino acids in the polypeptide chain requires activation. During this process, an enzyme known as aminoacyl-tRNA synthetase assists in attaching the amino acid to its corresponding tRNA. This reaction consumes one molecule of ATP, converting it into AMP and PP_i. Thus, for 200 amino acids, 200 ATP molecules are utilized.
• **Significance**: This activation step ensures that amino acids are ready and properly charged before being added to the growing protein chain. Without ATP, this essential activation simply wouldn't occur, stalling the entire synthesis process.

GTP Consumption

While ATP is crucial for amino acid activation, GTP (Guanosine Triphosphate) is vital during the translation phase of protein synthesis. Once amino acids are activated, the process shifts to elongating the polypeptide chain.
GTP is consumed primarily in two stages:

• **Peptide Bond Formation**: For each peptide bond created between adjacent amino acids, GTP is hydrolyzed to GDP. Since there are 199 peptide bonds in a 200-residue protein, 199 GTP molecules are expended here.
• **Ribosome Translocation**: After a peptide bond is formed, the ribosome shifts over the mRNA to read the next codon. This translocation also consumes one GTP molecule per shift. Therefore, another 200 GTP molecules are used here.
• **Total for Elongation**: Thus, the total GTP consumption for these two steps in elongation is 399 GTP molecules.

Amino Acid Activation

Amino acid activation is a critical preparatory step for protein synthesis where amino acids are attached to their respective tRNA molecules through the action of aminoacyl-tRNA synthetases. This complex reaction requires energy in the form of ATP.
Key points to understand:

• **Role of Aminoacyl-tRNA Synthetase**: This enzyme is responsible for recognizing specific amino acids and their corresponding tRNA. It catalyzes the binding of the amino acid to the tRNA, ensuring the right match.
• **Energy Requirement**: The reaction uses one ATP molecule, which is converted into AMP and pyrophosphate (PP_i). The use of ATP here is critical for driving the reaction forward efficiently.
• **Outcome**: Activated amino acids are now ready to be used during the synthesis of the protein, ensuring that the correct sequence of amino acids is added to the growing peptide chain.

Translation Initiation

Translation initiation is the first phase of protein synthesis where the ribosome assembles on the mRNA strand to start building the protein. This stage requires the concerted action of various factors and the consumption of GTP.
Important elements of this process include:

• **Formation of the Initiation Complex**: The small ribosomal subunit binds to the mRNA along with the initiator tRNA. Next, the large subunit joins to complete the initiation complex. The key energy source here is GTP, which is hydrolyzed once, aiding the assembly of this complex.
• **Initiator tRNA Role**: Identifies the starting codon on mRNA ensuring that the protein synthesis begins at the correct site.
• **Outcome**: A correctly assembled initiation complex is crucial for proper translation. A single GTP molecule is used during this entire process.

Peptide Bond Formation

Peptide bond formation is the fundamental chemical reaction in protein synthesis. This process links amino acids together into a polypeptide chain, forming the backbone of proteins.
A closer look into the process reveals:

• **Chemical Reaction**: Amino acids are joined by a covalent bond between the carboxyl group of one amino acid and the amino group of the next. An enzyme called peptidyl transferase, part of the ribosome's large subunit, catalyzes this reaction.
• **Role of Energy**: Although the actual formation doesn't involve direct energy consumption, the necessary positioning of the amino acids and tRNA within the ribosome is energetically driven by GTP hydrolysis during translation elongation.
• **Result**: This bond formation continues seamlessly, extending the polypeptide chain until the protein completion signal is reached.