The human body is capable of synthesizing some amino acids; others must be obtained through nutrition (essential amino acids). The amino acids phenylalanine, tryptophan, lysine, methionine, valine, leucine, isoleucine, histidine, and threonine belong to the essential amino acids.
Proteins often undergo posttranslational modification, by transferring oligosaccharide residues to asparagine (N‐glycosidic) or serine residues (O‐glycosidic) (see Section 5.4). Glycoproteins are found on the outside of the cell, in cell walls, and in the extracellular matrix, especially in connective tissue. Glycosylation is important for the biological activity and antigenic properties.
While the peptide bond itself is inflexible, the substituents at the α‐C atom of an amino acid can rotate freely. As a result, a polypeptide chain can engage in a number of spatial structures (conformations). Under aqueous conditions found in the cell, the polypeptide chains are not present in a linear form, but form spontaneous secondary and tertiary structures, which are energetically more favorable. These structures rely on many noncovalent bonds and forces; those that are important include the following:
Hydrogen bonds (bond strength of 4 kJ mol–1 under aqueous conditions).
Ionic bonds (electrostatic attraction) (bond strength of 12.5 kJ mol–1).
van der Waals forces (bond strength of 0.5 kJ mol–1).
Hydrophobic attractions.
Figure 2.8 summarizes the most common hydrogen bonds present in a cell. Electronegative atoms, such as oxygen and nitrogen, try to withdraw electrons from neighboring atoms such as hydrogen. This results in oxygen and nitrogen having a slight negative charge, while hydrogen is slightly positively charged. Positive and negative charges attract one another. The resulting attractions are known either as hydrogen bonds or as hydrogen bridges. The ability to form hydrogen bonds is especially present in water molecules (the hydrogens are positive; the oxygen atom is negatively charged), and water is therefore considered as the universal solvent of the cell. Biomolecules with polar groups easily take up water molecules (they are water soluble), while nonpolar residues repel water (hydrophobic) and group together with other apolar molecules (which are fat soluble). Figure 2.9 illustrates the importance of noncovalent and covalent bonds for the formation of protein folds. Through the formation of disulfide bridges between two cysteine residues, the conformation of a protein can also be covalently influenced (Figure 2.9).
Figure 2.8 Important hydrogen bonds in biomolecules.
Figure 2.9 Noncovalent bonds and disulfide bridges lead to a spatial folding and stabilization of a peptide. Bond types: hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges.
In comparison with covalent bonds (bond strength of 348–469 kJ mol–1), noncovalent bonds are 5–100 times weaker. When many noncovalent bonds are present, they simultaneously can work cooperatively, leading to the formation of stable and thermodynamically favored structure elements in polypeptides. Hydrophobic amino acid residues cluster together in order to lock water out. In polypeptides this can lead to a globular tertiary structure, while the hydrophobic residues are oriented toward the inside, and the polar and charged residues are oriented toward the outside (Figure 2.10). Under aqueous conditions, proteins usually fold spontaneously into a stable conformation in which the free energy is at the lowest.