Sickle cell anemia is a condition where red blood cells become sickle-shaped instead of disc-shaped. This is caused by the substitution of the polar glutamate with the nonpolar valine at the sixth position in the β subunit of hemoglobin A.

Proline is an amino acid that stands out from others due to its side chain and α-amino nitrogen forming a rigid, five-membered ring structure. Because of this unique geometry, proline is referred to as an "imino acid." While it contributes to the fibrous structure of collagen, it interrupts α-helices found in globular proteins.

Amino acids with uncharged polar side chains have no net charge at physiological pH. However, cysteine and tyrosine can lose a proton at alkaline pH. Serine, threonine, and tyrosine contain a polar hydroxyl group that can participate in hydrogen bond formation. Asparagine and glutamine have a carbonyl group and an amide group in their side chains, both of which can also engage in hydrogen bonding.

Cysteine contains a sulfhydryl (thiol) group, which is important in the active site of many enzymes. In proteins, two cysteines can form a disulfide bond, creating a covalent cross-link known as cystine. Disulfide bonds stabilize many extracellular proteins, including albumin, a blood protein responsible for transporting various molecules.

The polar hydroxyl group of serine, threonine, and sometimes tyrosine can serve as attachment sites for other structures such as a phosphate group. Additionally, the amide group of asparagine and the hydroxyl group of serine or threonine can act as attachment sites for oligosaccharide chains in glycoproteins.

Aspartic acid and glutamic acid are amino acids that act as proton donors. At physiological pH, their side chains are fully ionized, resulting in a negatively charged carboxylate group. These ionized forms are called aspartate and glutamate.

Amino acids with basic side chains, such as lysine and arginine, accept protons. At physiological pH, the R groups of lysine and arginine are fully ionized and carry a positive charge. On the other hand, histidine is weakly basic and mostly uncharged at physiological pH. However, when incorporated into a protein, the ionization state of histidine's R group can be either positive or neutral, depending on the protein's ionic environment. This property of histidine contributes to its buffering role in proteins like hemoglobin.

Commonly occurring amino acids are represented by letter symbols. The one-letter codes are determined by specific rules, such as using the unique first letter if only one amino acid begins with that letter (e.g., V for valine).
Sickle cell anemia, a disease of red blood cells that causes them to become sickle shaped rather than disc shaped, results from the replacement of polar glutamate with nonpolar valine at the sixth position in the β subunit of hemoglobin A (see p. 36).
2. Proline: Proline differs from other amino acids in that its side chain and α-amino nitrogen form a rigid, five-membered ring structure (Fig. 1.5).
Proline, then, has a secondary (rather than a primary) amino group. It is frequently referred to as an “imino acid.” The unique geometry of proline contributes to the formation of the fibrous structure of collagen (see p. 45), but it interrupts the α-helices found in globular proteins (see p. 16).
B. Amino acids with uncharged polar side chains
These amino acids have zero net charge at physiologic pH, although the side chains of cysteine and tyrosine can lose a proton at an alkaline pH (see Fig. 1.3). Serine, threonine, and tyrosine each contain a polar hydroxyl group that can participate in hydrogen bond formation (Fig. 1.6). The side chains of asparagine and glutamine each contain a carbonyl group and an amide group, both of which can also participate in hydrogen bonds.
1. Disulfide bond: The side chain of cysteine contains a sulfhydryl (thiol) group (−SH), which is an important component of the active site of many enzymes. In proteins, the –SH groups of two cysteines can be oxidized to form a covalent cross-link called a disulfide bond (−S–S–). Two disulfide-linked cysteines are referred to as cystine. (See p. 19 for a further discussion of disulfide bond formation.)
Many extracellular proteins are stabilized by disulfide bonds. Albumin, a blood protein that functions as a transporter for a variety of molecules, is an example.
2. Side chains as attachment sites for other compounds: The polar hydroxyl group of serine, threonine, and (rarely) tyrosine can serve as a site of attachment for structures such as a phosphate group. In addition, the amide group of asparagine, as well as the hydroxyl group of serine or threonine, can serve as a site of attachment for oligosaccharide chains in glycoproteins (see p. 165).
C. Amino acids with acidic side chains
The amino acids aspartic acid and glutamic acid are proton donors. At physiologic pH, the side chains of these amino acids are fully ionized, containing a negatively charged carboxylate group (−COO−). The fully ionized forms are called aspartate and glutamate.
D. Amino acids with basic side chains
The side chains of the basic amino acids accept protons (see Fig. 1.3). At physiologic pH, the R groups of lysine and arginine are fully ionized and positively charged. In contrast, the free amino acid histidine is weakly basic and largely uncharged at physiologic pH. However, when histidine is incorporated into a protein, its R group can be either positively charged (protonated) or neutral, depending on the ionic environment provided by the protein. This important property of histidine contributes to the buffering role it plays in the functioning of such proteins as hemoglobin (see p. 30). [Note: Histidine is the only amino acid with a side chain that can ionize within the physiologic pH range.]
E. Abbreviations and symbols for commonly occurring amino acids letter symbol (Fig. 1.7). The one-letter codes are determined by the following rules.
1.
Unique first letter: If only one amino acid begins with a given letter, then that letter is used as its symbol. For example, V = valine.
2.