FIGURE 7-19 Differential processing of preproglucagon by the pancreas and large intestine. The processing sites that must be cleaved to generate glucagon and the glucagon-like peptides are shown between indicated segments. The C-terminus of glucagon-like peptide 1 is amidated; the sequence Gly-Arg-Arg directs cleavage of the precursor and provides a substrate for the polypeptide-amidating activity enzyme complex (PAM). The tissue-specific processing of this precursor is indicated. In a-cells, processing predominates at the more N-terminally located Lys-Arg pairs to produce glucagon. In gut cells, residues 1-69 are released en bloc as glicentin or gut glucagon, whereas the C-terminal major proglucagon fragment (residues 70-160) is efficiently processed to release GLP-1 and -2 peptides. The arrows above the preproglucagon sequence at the top indicate the positions of introns in the human gene; each exon of the preproglucagon gene encodes a domain of the messenger RN A or of preproglucagon. The human glucagon gene, abbreviated CCG, is located on the long arm of chromosome 2 in the region q36-q37. [Modified with permission from Steiner, D. F., Bell, G. I., Tager, H. S., and Rubenstein, A. H. (1995). Chemistry and biosynthesis of the islet hormones: Insulin, islet amyloid polypeptide (amylin), glucagon, somatostatin and pancreatic polypeptide. In "Endocrinology" (L. J. DeGroot, M. Besser, H. G. Burger, J. L. Jameson, D. L. Loriaux, J. C. Marshall, W. D. Odell, J. T. Potts, Jr., and A. H. Rubenstein, eds.), 3rd ed., Vol. 2, Chapter 76, PP. 1296-1328. W. B. Saunders, Philadelphia, PA.]
Cleavage of signal peptide folding of prohormone
Propancreatic polypeptide igkr
Dibasic processing Carboxypeptidase E removal of basic residues
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