Editing Proinsulin (section)

== Synthesis and Post-translational Modification ==

Proinsulin is synthesized on membrane associated ribosomes found on the [[rough endoplasmic reticulum]], where it is folded and its [[disulfide bond]]s are oxidized. It is then transported to the [[Golgi apparatus]] where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature [[insulin]]. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the [[C-peptide]]. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds.{{cn|date=November 2023}}

The [[Post-translational modification|post translational modification]] of proinsulin to mature insulin only occurs in the beta cells of the pancreatic islets.<ref>{{cite journal | vauthors = Groskreutz DJ, Sliwkowski MX, Gorman CM | title = Genetically engineered proinsulin constitutively processed and secreted as mature, active insulin | journal = The Journal of Biological Chemistry | volume = 269 | issue = 8 | pages = 6241–5 | date = February 1994 | doi = 10.1016/S0021-9258(17)37593-2 | pmid = 8119968 | url = http://www.jbc.org/content/269/8/6241.full.pdf | doi-access = free }}</ref> When proinsulin is transported through the Golgi apparatus the C-peptide is cleaved.<ref name="Weiss_2009"/> This cleavage occurs with the aid of two endoproteases.<ref name="Kaufmann_1995">{{cite journal | vauthors = Kaufmann JE, Irminger JC, Halban PA | title = Sequence requirements for proinsulin processing at the B-chain/C-peptide junction | journal = The Biochemical Journal | volume = 310 | issue = 3 | pages = 869–74 | date = September 1995 | pmid = 7575420 | pmc = 1135976 | doi = 10.1042/bj3100869 }}</ref> Type I [[endoprotease]]s, [[Proprotein convertase 1|PC1]] and PC3, disrupt the C peptide-B chain connection.<ref name="Kaufmann_1995" /> PC2, a type II endoprotease, cleaves the C peptide-A chain bond.<ref name="Kaufmann_1995" /> The resulting molecule, now mature insulin, is stored as a hexamer in [[secretory vesicles]] and is stabilized with <math>Zn^{2+} </math> ions until it is secreted.<ref name="Weiss_2009"/>
[[File:Proinsulin evolution.png|frameless|center|upright=2.5|class=skin-invert-image]]