Effect of the insulin iodination on the reactivity of the inter-chain disulphide bonds towards sodium sulphite.

Insulin iodination interferes with the ability of the interchain S.S bonds to react with sulphite at pH7. In insulin samples containing more than 5 iodine atoms/monomer unit, only one S.S bond/molecule reacts. The effect must be related to the substitution of the iodine into the tyrosyl groups, which probably causes a conformational rearrangement resulting in a steric hindrance of one of the interchain S.S bonds. The effect is removed by increasing the pH or by adding urea (8m) to the reaction mixture. The unreactivity of the S.S bond and the biological inactivation occur at the same ;critical' iodination level, suggesting that a same primary alteration of the molecule is responsible for both the effects.