The peptide hormone insulin is secreted from a pancreatic ce

The peptide hormone insulin is secreted from a pancreatic cell. Describe the pathway that traces the movement from its site of synthesis to the outside of a eukaryotic cell. Identify all of the organelles that the protein passes through, describe what happens in each of the organelles, and indicate the direction of movement.

Solution

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Insulin is synthesized in the pancreas within the -cells of the pancreas. Within the islets of Langerhans, beta cells constitute 65–80% of all the cells.

Insulin is first synthesized as a single polypeptide called preproinsulin in pancreatic -cells. Preproinsulin contains a 24-residue signal peptide which directs the nascent polypeptide chain to the rough endoplasmic reticulum. The signal peptide is cleaved as the polypeptide is translocated into lumen of the RER, forming proinsulin In the RER the proinsulin folds into the correct conformation and 3 disulfide bonds are formed. About 5–10 min after its assembly in the endoplasmic reticulum, proinsulin is transported to the trans-Golgi network where immature granules are formed. Transport to the TGN may take about 30 min.

Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases, as well as the exoprotease carboxypeptidase E. The endopeptidases cleave at 2 positions, releasing a fragment called the C-peptide, and leaving 2 peptide chains, the B- and A- chains, linked by 2 disulfide bonds. The cleavage sites are each located after a pair of basic residues. After cleavage of the C-peptide, these 2 pairs of basic residues are removed by the carboxypeptidase. The C-peptide is the central portion of proinsulin.

The resulting mature insulin is packaged inside mature granules. These mature gransules are waiting for metabolic signals and vagal nerve stimulation to be exocytosed from the cell into the circulation.

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