Parathyroid hormone biosynthesis: structure and function of biosynthetic precursors

Investigations over the past several years have uncovered new information concerning the processes involved in the cellular formation of parathyroid hormone (PTH). Studies of parathyroid hormone biosynthesis in vitro using intact cell preparations as well as cell-free systems have led to: identification and characterization of a biosynthetic pathway for the formation of PTH involving successive proteolytic cleavages of the hormone from a larger polypeptide precursor; identification of the subcellular locations where the proteolytic processing of the precursors takes place; isolation of the messenger RNA for the hormone; and, finally, synthesis of functionally active gene copy of the parathyroid mRNA. It is now generally recognized that biosynthetic precursors and their post-translational modifications by proteolytic cleavages are characteristic of the biosynthetic processes involved in the formation of most if not all secretory proteins, not only parathyroid hormone and other polypeptide and protein hormones, but such diverse proteins as immunoglobulins, enzymes, and albumin. Furthermore, it is now evident that these biosynthetic precursors belong to two distinct classes, preproteins and proproteins, based on several criterions, including i) the time that elapses between synthesis of the precursor and the proteolytic conversion to the product, ii) the subcellular site at which the cleavages occur, iii) the specificity of the enzymic cleavage, and iv) the characteristics of the primary structures of the precursors.