Chemistry and biosynthesis of pro-opiomelanocortin. ACTH, MSH's, endorphins and their related peptides.
Studies of lipotropins, melanotropins and endorphins on one hand, and of adrenocorticotropin on the other, has given rise to the concept of a multipotent precursor molecule recently renamed proopiomelanocortin. The preferential sites of cleavage of the precursor to produce its biologically active components are made of pairs of basic amino acid residues as described for the biosynthesis of beta-MSH and pro-insulin. Such structural feature is also found in other pro-hormone molecules. Pulse chase experiments and secretory studies carried out in both anterior and intermediate lobes of rat pituitary glands revealed the transformation of different forms of the precursor into different end-products, the anterior lobe producing preferentially ACTH and beta-LPH while the intermediate produces mainly the alpha-MSH and beta-endorphin. The multiple forms of precursors seem to differ in their carbohydrate content although at least two different gene products are still possible. The presence of similar peptides in the hypothalamus makes it highly probable that neuropeptides are biosynthesized with similar process. Thus the model of beta-LPH precursor, proposed as early as in 1967, is now applicable to the biosynthesis of all other neuropeptides. Major advances in this field are expected in the 1980s.
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001923:Brain Chemistry; D002417:Cattle; D004723:Endorphins / Q000302:isolation & purification; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis*; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000502:physiology*; D011333:Pro-Opiomelanocortin; D011384:Proinsulin / Q000378:metabolism; D011487:Protein Conformation; D011498:Protein Precursors / Q000502:physiology*; D051381:Rats; D008083:beta-Lipotropin / Q000096:biosynthesis*
D004723:Endorphins; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D008083:beta-Lipotropin; D011384:Proinsulin