disulfide

Meaning: A disulfide bond (R–S–S–R) joins the sulfur atoms of two cysteine side chains. The oxidized pair is called cystine. Forming the bond is an oxidation of the thiols, and breaking it is a reduction. Because it is covalent, it is far stronger than the hydrogen bonds, ionic interactions and hydrophobic effects that mostly hold tertiary structure. It can link distant parts of one chain (tertiary structure) or separate chains (quaternary structure, as in antibodies and insulin). Disulfides form mostly in the oxidizing environment of the endoplasmic reticulum and in extracellular space, and are less common in the reducing cytosol.

Equation: 2 R–SH ⇌ R–S–S–R + 2H⁺ + 2e⁻, where R is the rest of the cysteine side chain, H⁺ is a proton and e⁻ is an electron (amounts in mol). Moving right is oxidation; moving left is reduction.

On the MCAT: Expect a passage where a reducing agent (β-mercaptoethanol, DTT) unfolds a protein or splits its chains on a gel, and you predict lost activity or changed band pattern. Other questions ask which amino acid forms the bond or which level of structure it stabilizes.

Common confusion: Disulfide bonds are not part of secondary structure, which depends on backbone hydrogen bonds. Methionine also contains sulfur, but its thioether has no –SH and cannot form a disulfide. Only cysteine does.