Cellular processing of pre-proparathyroid hormone involves rapid hydrolysis of the leader sequence.
The cellular synthesis of parathyroid hormone (PTH) involves two consecutive cleavages of NH2-terminal peptide sequences from a larger precursor, pre-proparathyroid hormone (Pre-ProPTH). The initial cleavage consists of the removal of an NH2-terminal leader sequence either during or shortly after biosynthesis of the polypeptide chain is complete. To determine the fate of the cleaved leader sequence, we prepared, by chemical synthesis, a peptide based on the known structure of the leader sequence of pre-proparathyroid hormone and used this peptide labeled with 125iodine as a marker to monitor the recovery of the putative cellular leader peptide during extraction and electrophoresis of [35S]methionine-labeled proteins from pulse-labeled parathyroid gland slices. Under conditions in which the recovery of the synthetic leader peptide was 50 to 70%, we found no detectable 35S-labeled product in the region of sodium dodecyl sulfate gels where the synthetic peptide migrates. In view of the known methionine content of pre-proparathyroid hormone and proparathyroid hormone (ProPTH), it would have been possible to detect endogenously labeled leader peptide if present in amounts equal to 0.05% of the amount of labeled ProPTH present in the tissues. These observations indicate that the cellular conversion of Pre-ProPTH to ProPTH involves a rapid hydrolysis of the leader peptide either during or immediately after its removal from the precursor.
D000818:Animals; D002417:Cattle; D006868:Hydrolysis; D008715:Methionine / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000096:biosynthesis*; D010455:Peptides / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis*
D010281:Parathyroid Hormone; D010455:Peptides; D011498:Protein Precursors; D008715:Methionine