Biomolecules: Structure and Function

Amino acid pKa and isoelectric point

Each ionizable group of an amino acid has its own pKa, which is the pH at which half of that group is dissociated. The pKa values determine the net charge of the molecule at any pH. In a free amino acid, the α-carboxyl group dissociates with a pKa near 2, and the α-amino group with a pKa near 9 to 10, so the zwitterionic form predominates near neutral pH. Side chains can add further ionizable groups. The guanidinium group of arginine is a strong base with a pKa of about 12.5, so it stays protonated and positively charged across the whole physiological pH range. The imidazole ring of histidine has a pKa close to 6, which is why histidine contributes buffering capacity near neutral pH.

The isoelectric point, pI, is the pH at which the net charge of the amino acid is zero. For an amino acid whose side chain is not ionizable, the pI is the average of the two pKa values that flank the zwitterionic form, namely the pKa of the α-carboxyl group and the pKa of the α-amino group. Thus \text{pI} = \frac{pK_1 + pK_2}{2}. For example, if the two pKa values are 2.0 and 10.0, the pI is 6.0.

The number of acid-base groups depends on whether the side chain is ionizable. Tyrosine has an α-amino group, an α-carboxyl group and a phenolic hydroxyl group in its side chain, so it has three acid-base groups in total. Alanine, leucine and phenylalanine have only the α-amino and α-carboxyl groups, because their side chains are not ionizable. Students should therefore check the side chain first when counting ionizable groups.

Carbohydrate stereochemistry and glycosidic linkages

Epimers are diastereomers that differ in the configuration of exactly one stereocentre. Aldoses and ketoses with the same molecular formula are structural isomers rather than epimers, because their carbonyl groups are located differently. For example, glucose and mannose differ only at C-2, and glucose and galactose differ only at C-4, so each pair is an epimeric pair. Glucose and fructose, by contrast, are structural isomers because fructose is a ketose.

A glycosidic linkage is described by the anomeric configuration (α or β) and the carbon positions that are joined, such as 1→4. A β1→4 linkage joins the anomeric carbon of one sugar in the β configuration to the C-4 hydroxyl of the next sugar. Cellulose, chitin and lactose all contain β1→4 linkages, whereas maltose contains an α1→4 linkage.

Polysaccharides are classified as homopolysaccharides when they contain only one kind of monosaccharide, and as heteropolysaccharides when they contain more than one kind. Chitin and cellulose are homopolymers, although both have β1→4 linkages. Chondroitin-4-sulfate and heparin are heteropolysaccharides, because they are built from repeating disaccharide units that contain uronic acid and an amino sugar.

Lipid structure and classification

Lipids are often described as amphipathic, meaning that they have both a polar region and a nonpolar region. Cholesterol illustrates this property well, because its hydroxyl group at one end is polar while its steroid ring system and hydrocarbon tail are hydrophobic. Phospholipids spontaneously self-assemble into bilayers or micelles in water, and this process is driven by the hydrophobic effect, in which the nonpolar fatty acyl tails are excluded from water.

The degree of unsaturation of fatty acyl chains affects membrane physical properties. Each cis double bond introduces a kink that disrupts tight packing of the acyl chains, so the gel-to-liquid crystalline transition temperature decreases as unsaturation increases. The choline head group of phosphatidylcholine carries a quaternary ammonium group with a permanent positive charge, while the phosphate group carries a negative charge, so the net charge of the lipid can be zero.