thiol

Meaning: A thiol is the functional group R–SH, the sulfur analog of an alcohol. In proteins it is the side chain of cysteine. Sulfur is larger and more polarizable than oxygen, so thiols are more acidic than alcohols and form weaker hydrogen bonds. The deprotonated form, thiolate (R–S⁻), is a strong nucleophile.

Equation: 2 R–SH ⇌ R–S–S–R + 2H⁺ + 2e⁻, where R is the rest of the molecule, R–S–S–R is a disulfide, H⁺ is a proton and e⁻ is an electron. The forward direction is oxidation and the reverse is reduction. No SI units apply.

On the MCAT: Passages describe disulfide bridges stabilizing tertiary or quaternary structure, especially in secreted or extracellular proteins such as antibodies and insulin. Adding a reducing agent such as β-mercaptoethanol or dithiothreitol breaks disulfides, so subunits separate on SDS-PAGE. Expect questions on the effect of mutating a cysteine. Cysteine thiolates also act as nucleophiles in some enzyme active sites.

Common confusion: Methionine also contains sulfur, but as a thioether with no S–H, so it cannot form a disulfide. A disulfide bond forms between two cysteines by oxidation, not by dehydration or hydrolysis.