In: Biology
Describe the events that occur during the manufacture and secretion of the insulin protein in a pancreatic cell (eukaryotic cell). Begin with expression of the insulin gene. Be sure you describe the transcription, processing, and translation steps, giving detail for the initiation stage of transcription and translation (what features of DNA and RNA tell the machinery where to start and what machinery is involved). Once the protein is translated, describe the pathway and cellular organelles involved in the transport of the protein to a final destination (extracellular secretion). For each organelle you identify, briefly describe what happens to the protein while it is in that organelle. (Biological Synthesis)
Insulin has a small molecular weight that is about 6kDa. There are two chains joined by a disulfide bond. This sequence is synthesised in the beta cells in the islet of langerhans. The mRNA of insulin would be translated in the form of a single chain along with removal of the peptide which would take place at the time of insertion in the endoplasmic reticulum resulting in proinsulin. There are 3 domains in the b chain consisting of an amino terminal and the a chain. There is presence of a c peptide that acts as the connecting peptide.
In the endoplasmic reticulum, proinsulin would be getting exposed to the different endopeptidases that would be removing the C peptide. After the excision of the C peptide, there would be generation of the mature insulin. The insulin as well as the excised C peptide would be packed inside the Golgi apparatus inside the secretory granules that would be accumulating in cytoplasm.
As beta cells would be stimulated appropriately, insulin would be secreted via the method of exocytosis and would be diffusing in the cappilarh blood present in the islet cells. C peptide will also be secreted inside blood but will not be having any biological activity.
The secretion of insulin would be in response to the increased blood glucose levels, this is because insulin carries out facilitation of the entry of glucose in the cells. Neural stimulus along with the concentration of glucose in blood, along with the fat cells are some of the stimuli of secretion of insulin.
Initiation factor is the eIF4E that will be binding to the 5’ end of mRNA mediating initiation factor complex assembly. This assembly is also regulated by the 4E-BPs , which would be inhibiting the assembly of the complex. Insulin would be inducing 4E -BPs phosphorylation and inhibition would be alleviated. The 5’UTR region has a secondary structure. Overall translation stimulation involves initiation activation of the factor eIF2B, that is necessary for the different events of initiation.
Elongation of the peptide chain is also done by insulin through dephosphorylation of eF2.