The mode of conversion of proparathormone to parathormone by a particulate converting enzymic activity of the parathyroid gland

• Published in: The Journal of biological chemistry 1978-03, Vol.253 (6), p.2012-2017
• Main Authors: MacGregor, R R, Hamilton, J W, Cohn, D V
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cattle; Kinetics; Parathyroid Glands - enzymology; Parathyroid Hormone - biosynthesis; Peptide Hydrolases - metabolism; Protein Precursors - metabolism; Substrate Specificity; Swine
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)62348-3

The cleavage products from the conversion of proparathormone to parathormone by a bovine and porcine parathyroid microsomal converting activity have been analyzed. In the conversion reaction, the first 6 amino acid residues of the prohormone (Lys-Ser-Val-Lys-Lys-Arg-) are released as an intact hexapeptide. This is rapidly converted to a pentapeptide by removal of the NH2-terminal lysine and then to a tetrapeptide by removal of the COOH-terminal arginine. In order to test for the presence of a postulated COOH-terminal extension of the parathormone sequence in proparathormone, mixtures of 14C-proparathormone and 3H-parathormone were subjected to digestion by trypsin or Staphylococcus aureus protease. The resulting radioactive peptides from the hormone and its precursor were compared. There was no evidence that any fragments different from those from the hormone were released from the prohormone except those accounted for by the NH2-terminal hexapeptide adduct on proparathormone. Thus, the conversion of the prohormone to the hormone catalyzed by the microsomal membrane activity requires only the cleavage of this hexapeptide.