Sign up

Organic chemistry · Lesson 6

The shape of life

Proteins are polyamides made from amino acids, and their shape is everything. Four levels of structure, why heat and pH wreck them, and how enzymes speed up the chemistry of life.

Crack an egg into a hot pan and the clear, runny white turns solid and opaque in seconds. Nothing has been added and nothing has boiled away. The protein molecules in the egg white have simply lost their shape: they have been denatured. Cool the pan and the egg does not turn clear again.

The same thing can happen inside you. Your body’s chemistry runs on enzymes, protein catalysts whose shapes must be exactly right to work. A few degrees above normal body temperature and they start to lose that shape, which is one reason a very high fever is a medical emergency.

Laundry manufacturers exploit enzymes too, adding proteases and lipases that digest protein and fat stains at low wash temperatures. This lesson builds proteins up from amino acids and explains how their shape, and therefore their function, depends on intermolecular forces.

Amino acids

The amino acids in proteins are 2-amino acids: an amine group and a carboxylic acid group attached to the same carbon, which also carries a hydrogen atom and a side chain, R. General formula: H2N-CH(R)-COOH. About twenty R groups occur in proteins: non-polar (glycine, R = H; alanine, R = CH3), polar (serine, R = CH2OH), acidic (aspartic acid, R contains –COOH), basic (lysine, R contains -NH2), and cysteine, whose R group contains –SH.

In water, the acidic –COOH donates a proton to the basic -NH2 of the same molecule, forming a zwitterion, H3N+-CH(R)-COO−, which has both charges. In strong acid it is protonated to a cation (H3N+-CH(R)-COOH); in strong base it becomes an anion (H2N-CH(R)-COO−). That is why amino acids are crystalline solids with high melting points.

Peptide bonds

The –COOH of one amino acid reacts with the -NH2 of the next, releasing water and forming an amide link, called a peptide bond (–CO–NH–). Two amino acids give a dipeptide; many give a polypeptide. A protein is one or more polypeptide chains, usually hundreds of amino acids long: a condensation polymer. Hydrolysis (with acid, or with enzymes during digestion) breaks the peptide bonds again.

Four levels of protein structure

  • Primary: the sequence of amino acids, held by covalent peptide bonds.
  • Secondary: regular folding of the backbone into an α-helix or a β-pleated sheet, held by hydrogen bonds between the C=O of one peptide group and the N–H of another.
  • Tertiary: the overall three-dimensional shape of the chain, held by interactions between R groups: hydrogen bonds, ionic attractions (between -COO− and -NH3+ groups), disulfide bridges (covalent S–S bonds between cysteines) and dispersion forces between non-polar R groups, which cluster away from water.
  • Quaternary: two or more chains fitted together, as in haemoglobin (four chains).

Denaturation is the loss of secondary and tertiary structure when heat, extreme pH or heavy-metal ions disrupt the hydrogen bonds, ionic attractions and other interactions. The primary structure is unchanged, because peptide bonds are not broken, but the protein loses its shape and its function.

Enzymes

Enzymes are proteins that act as biological catalysts: like any catalyst, they provide a pathway with a lower activation energy. The substrate binds to a small region, the active site, whose shape and R groups match it. That makes enzymes highly specific: catalase breaks down hydrogen peroxide and nothing else.

  • Temperature: as it rises, the rate increases (more frequent, more energetic collisions), up to an optimum; above that, the enzyme denatures, the active site changes shape and the rate falls sharply.
  • pH: each enzyme has an optimum pH (pepsin in the stomach about 2; catalase about 7). Away from it, the charges on R groups change, ionic attractions and hydrogen bonds are disrupted, and the active site loses its shape.
Loading the 3D model…

Experiment: catalase and temperature

Liver pieces in hydrogen peroxide at five temperatures, plus a boiled-liver control. Start the experiment, then repeat it at pH 3 and pH 11.

Explaining denaturation for full marks

  1. Name the change (heat, pH) and the interactions it disrupts: hydrogen bonds, ionic attractions (and dispersion forces) between R groups and along the backbone.
  2. State that the secondary and tertiary structure is lost, but the primary structure (peptide bonds) remains.
  3. For an enzyme: the active site changes shape, so the substrate no longer fits and the rate falls.
Now put it to workFive worked examples, twenty practice questions and ten harder problems on this lesson.
Go to the questions