Post-translational Modification of preproinsulin to biologically-active insulin

         Preproinsulin is initially translated as a 110 amino acid molecule, comprising a signal peptide and B-, C- & A-chains. The signal peptide (24 aa's) is first clipped from amino terminus. The A- & B- Chains of the proinsulin are then joined by disulfide bridges. This stabilizes the molecule so that the intervening C peptide (35 aa's) can be excised. The biologically-active, tertiary structure of insulin comprises an A chain (30 aa's) & B chain (21 aa's) held together by 3 disulfide bridges. [One S-S bridge that joins two cys residues in the A-Chain is not shown].


    A patient was admitted to the emergency room of a hospital in insulin shock. Radioimmunoassay showed high levels of insulin in the blood. Physicians first suspected an insulinoma, a cancer of the pancreas that would cause it to over-secrete insulin. However, the biopsy was negative, and the patient was released. Several weeks later, the patient again showed up in insulin shock. This time, the lab adjusted the RIA to detect preproinsulin as well as insulin. The patient tested postive for insulin as before, and tested negative for preproinsulin.

Suggest a hypothesis to explain these results.

Figure ©2012 TA Brown, Introduction to Genetics (1st ed.); additional text ©2014 by Steven M. Carr