Principles of Protein Structural Organization - H. Schultz 1982

The Structural Role of the Peptide Bond
Synthesis on Ribosomes

Polypeptides are formed through a series of highly specific reactions. Amino Acids are incorporated into the polypeptide chain on cellular Ribosomes. Polymerization is based on The formation of amide bonds, commonly referred to as peptide bonds. The direction of the chain is conventionally defined from the amino terminus (N-terminus) to the carboxyl terminus (C-terminus), as illustrated in Fig. 2.2. This corresponds to the direction of chain synthesis in vivo, which in turn mirrors the 5' → 3' direction of Messenger RNA.

Free energy governs fidelity. The formation of a single peptide bond entails the Cleavage of four high-energy bonds from adenosine triphosphate (ATP) and guanosine triphosphate (GTP) [22], releasing approximately 25 kcal per mole of amino acid [23]. Only a fraction of this energy is consumed in driving the peptide bond formation—an endergonic reaction with a Standard Free Energy in Water of about 5 kcal/mol [24]. The remaining energy is utilized to translate the messenger RNA sequence into a polypeptide and to ensure maximum translational accuracy. Hydrolytic cleavage of peptide bonds is prevented by a high activation energy barrier, which is nevertheless readily overcome by numerous protein-degrading Enzymes (proteases).

The low energy required for bond formation enables rapid ADAPTATION TO ENVIRONMENTAL shifts. From a structural standpoint, the peptide bond is exceptionally advantageous because it can be both synthesized and cleaved at a relatively low energy cost. This significantly enhances an Organism's capacity to redirect its resources into required forms, thereby providing a more efficient and robust defense against adverse environmental fluctuations. In the case of much stronger bonds, such as those found in the aliphatic tails of Fatty acids, adaptive responses would be far slower, ultimately reducing the evolutionary competitiveness and adaptability of organisms.