Question

Mention the chemical change that proinsulin undergoes, to be able to act as mature insulin.

Answer 1

Insulin is a peptide hormone that is secreted by the beta cells of the pancreas. It regulates the metabolism of carbohydrates by enhancing the absorption of glucose from the blood. The human insulin consists of 51 amino acids and is a heterodimer consisting of two polypeptide chains linked by disulfide bridges. However, insulin is not secreted in its mature form. Some chemical changes precede the formation of mature insulin from proinsulin.

Complete answer:
Insulin is first synthesized as a single polypeptide called preproinsulin. This contains a signal peptide that helps the polypeptide reach the endoplasmic reticulum. While translocating into the lumen of the rough endoplasmic reticulum, the signal peptide is cleaved to form the proinsulin. Proinsulin attains the correct conformation by the formation of three disulfide bonds and gets transported to the Golgi complex where it undergoes maturation to insulin.
Active insulin is formed by the action of an endopeptidase, prohormone convertase, and an exopeptidase, carboxypeptidase. The action of the endopeptidase helps release a fragment of the polypeptide called the C-peptide. It is the central portion of the proinsulin. The resulting mature insulin is packaged in granules. Once an appropriate signal is received the granules are exocytosed and released into the bloodstream.

Note: Insulin is known to be produced in the brain. Thus the deficiency of insulin or its related proteins in the brain leads to Alzheimer’s disease. Other hormones like glucagon, cortisol, and growth hormone antagonize the effects of insulin. The release of insulin is inhibited by norepinephrine which leads to increased blood glucose level during stress.