The intracellular pathway for parathormone biosynthesis and secretion.
The initial translation product of parathormone messenger RNA--preproparathormone--is larger than parathormone. Two amino terminal peptide segments of the peptide chain are removed sequentially to form the 84-amino acid hormone. The first cleavage, the removal of a 25-amino acid extension from preproparathormone, occurs in the rough endoplasmic reticulum, and results in the formation of proparathormone. This peptide moves via an energy-dependent mechanism to the Golgi region of the cell where a specific converting enzyme cleaves a basic hexapeptide segment yielding parathormone itself. A part of the newly formed hormone then is enclosed within prosecretory vesicles, transported to the cellular membrane and secreted. Another portion is stored in mature secretory vesicles and is subject to subsequent secretion. The moment to moment control of parathormone secretion by calcium resides at the plasma membrane, but a tightly coupled response at the level of intracellular hormone degradation is also necessary in order to control intracellular hormone levels in the face of rapid changes in secretory rate. Three major secretory products are released from the parathyroid under the control of extracellular calcium: (1) parathormone, (2) a large protein--"parathyroid secretory protein"--whose function is unknown, and (3) peptide fragments of parathormone. Secretion of hormonal fragments adds to the population of parathormone immunoreactivity in the blood. These fragments appear to be similar if not identical to those formed by peripheral metabolism of parathormone in the liver and kidney.
D002118:Calcium / Q000097:blood; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D010447:Peptide Hydrolases; D002118:Calcium