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The Mechanism of Insulin Biosynthesis by Pancreatic -cells

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⚡ Welcome to Catalyst University! I am Kevin Tokoph, PT, DPT.

Welcome back to catalyst university my name is kevin toke off please make sure to like this video and subscribe to my channel for future videos and notifications in this video we’re going to discuss the processing of insulin how we generate mature insulin and this is going to require the secretory system so that’s going to be the endoplasmic reticulum particularly

The rough er so i should probably make a note of that and then the golgi apparatus so in the previous video we talked about the mechanism by which the pancreatic beta-cell detects glucose in the blood and then creates an insulin release proportional with that amount of glucose and the insulin was packaged into these insulin granules for direct release into the

Blood but this process of getting them into the granules is a more complicated process and that’s what i mentioned or hinted to in the previous video now let’s talk about how this actually occurs and what we need to understand is there’s really three forms of insulin so to speak we have the the form of insulin that’s directly made by the ribosome this is called

Pre pro insulin once we actually take the cysteine residues and oxidize them into disulfide bridges which you have to do to generate mature insulin this is called pro insulin and that’s the first step the second step is to actually get completely mature insulin and to do that you have to cleave off this large protein component which is called the c peptide and

Then this is going to be mature insulin okay there’s a couple other minor steps we’re gonna have to do and we’re going to look at those in this diagram over here now because insulin is not going to be a cytosol of protein it’s gonna have to be released outside the cell it’s gonna require the secretory pathway and since ribosomes make protein and it’s gonna be

Involved in that pathway the ribosomes are gonna be attached to the rough er so that’s going to be this ribosome right here large and small subunit and this is the membrane of the rough er what you can see here is the ribosome is going to generate this protein insulin it’s actually going to be pre pro insulin and you can see that it’s being fed into the lumen

Of the rough er so remember the er is a membrane-bound organelle and it has an inside that’s the lumen that’s where the majority of this process is gonna occur so we have to have translation of the mrna that makes pre-pro insulin and then it’s ultimately good as you can see translocated into the lumen of the rough er okay now once this protein it’s immature its

Pre pro insulin once it’s inside the rough er lumen we’re gonna have folding which is obvious proteins have to fold oxidation and signal peptide cleavage so first of all what’s the signal peptide well the signal peptide is a region of the protein that’s going to ultimately signal that it needs to go into the rough er lumen and any protein when it’s translated

Initially that needs to go into the rough er lumen is always going to have this signal sequence the signal sequence is never a part of the mature protein so it has to be cleaved off okay that cleavage is going to be catalyzed by this protein called sec 11 okay so this is going to be a protease that cleaves off the signal sequence also we have to have oxidation so

The oxidation is referring to the disulfide bridges that have to form so we would initially just have three cysteine files but those have to be oxidized as shown right here into disulfide bridges that’s a process that’s going to occur in the rough er lumen and so once you have all three of those things removal of the signal peptide obviously the folding and then

All three of the disulfide bridges then this pro insulin now as it was called is going to be moved into the golgi apparatus okay the golgi apparatus is this part of this picture right here that’s closest to the insulin granules from here the remaining steps are going to occur in a vesicle that’s actually generated by the golgi apparatus so we have now pro insulin

Okay but we’re gonna have to cleave off this c peptide and notice we’re gonna have to cleave it in two spots in this picture one up here at the top and then one down here at the bottom that’s going to remove all this the c peptide this is going to be catalyzed by two different proteases both of which are termed hormone convertase azure pro protein convert asus and

This one is pro hormone convertase to this is either prohormone convert taste 1 or 3 these are golgi enzymes they’re gonna wind up in the secretory vesicle and they’re gonna have to cleave off this c peptide as shown right here okay once you do that there’s one more step we actually are gonna have to cleave off a couple of amino acid residues at the c terminal

End this is catalyzed by carboxypeptidase ii and once you cleave off these two amino acids at the c terminus then you have mature insulin okay so like i said in this video it’s a lot more complicated than just having an mrna translating it to insulin no we actually initially generate pre pro insulin from the mrna this is going to be fed into the er lumen it’s

Going to be folded disulfide bridges are gonna form through oxidation in the lumen and then we’re gonna cleave off that signal sequence that’s going to be characteristic of any protein in the er then it’s going to be transported to the golgi packaged into a vesicle and then we’re gonna have a couple other transformations one removal of the c peptide which is

Catalyzed by prohormone convert aces and then removal of a couple c terminal amino acids by carboxypeptidase ii that’s going to give you mature insulin and once that’s accomplished as i mentioned in the previous video that insulin can then be released into the blood in proportion to the amount of glucose in the blood and if you need more review on that go back

And watch the previous video but remember that this initial release of insulin into the blood directly at least is triggered by the level of intracellular calcium so the more calcium you have the more insolence released and so you can get a graded response but in any case i hope you enjoyed this video and learned a lot please make sure to like this video and

Subscribe to my channel for future videos and notifications thank you

Transcribed from video
The Mechanism of Insulin Biosynthesis by Pancreatic β-cells By Catalyst University