Peptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and degraded by extracellular proteases.
Insulin processing occurs in 4 steps: formation of intramolecular disulfide bonds, formation of proinsulin-zinc-calcium complexes, proteolytic cleavage of proinsulin by PCSK1 (PC1/3) and PCSK2 to yield insulin, translocation of the granules across the cytosol to the plasma membrane.
During Synthesis, secretion, and deacetylation of Ghrelin, proghrelin is acylated by ghrelin O-acyltransferase and cleaved by PCSK1 to yield the mature acyl ghrelin and C-ghrelin. In the bloodstream acyl ghrelin is deacylated by butyrylcholinesterase and platelet-activating factor acetylhydrolase.
During Metabolism of Angiotensinogen to Angiotensin, Renin cleaves angiotensinogen to yield a decapaptide, angiotensin I (angiotensin-1, angiotensin-(1-10)). Two C-terminal amino acid residues of angiotensin I are then removed by angiotensin-converting enzyme (ACE), located on the surface of endothelial cells, to yield angiotensin II (angiotensin-2, angiotensin-(1-8)), the active peptide that causes vasoconstriction, resorption of sodium and chloride, excretion of potassium, water retention, and aldosterone secretion. More recently other, more tissue-localized pathways leading to angiotensin II and alternative derivatives of angiotensinogen have been identified and described.
Incretin synthesis, secretion, and inactivation occurs through processing of incretin precursors (preproGLP-1 and preproGIP) by PCSK1. After secretion both incretins (GLP-1 and GIP) can be inactivated by cleavage by DPP4.
Peptide hormone biosynthesis describes processing of glycoprotein hormones (those which include carbohydrate side-chains) and corticotropin.