The physical chemistry of the insulin molecule in solution is reviewed. The nature of the self-association behavior is such that at physiological concentration levels insulin must exist as a monomer even in the presence of zinc. Analysis of the data on the interaction between zinc and insulin in solution leads to the conclusion that the zinc insulin complex formed has a conformation very similar to the x-ray structure of crystalline zinc insulin. Conformational studies on insulin and proinsulin support the following structural model—the insulin portion of the proinsulin molecule is in the same conformation as the free insulin molecule. Finally, studies indicate that the α-NH2 group on the A1 glycine of insulin is very important for biological activity.

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