PTH Is Secreted as an 84-Amino-Acid Peptide
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p502
2025-11-16
55
The immediate precursor of parathyroid (PTH) is proPTH, which differs from the native 84-amino-acid hormone by having a highly basic hexapeptide amino terminal extension. The primary gene product and the immediate precursor for proPTH is the 115-amino-acid preproPTH. This differs from proPTH by having an additional 25-amino-acid NH2-terminal extension that is common with the other leader or signal sequences characteristic of secreted proteins; it is predominantly hydrophobic in nature. The complete structure of pre proPTH and the sequences of proPTH and PTH are illustrated in Figure 1. PTH1–34 has full biologic activity, and the region 25 to 34 is primarily responsible for receptor binding.
Fig1. Structure of bovine preproparathyroid hormone. The green arrows indicate sites of cleavage by processing enzymes in the parathyroid gland and in the liver after secretion of the hormone (numbered 1 to 5). The biologically active region of the molecule (colored) is flanked by sequence not required for activity on target receptors. (Reproduced with permission from Habener JF. Recent advances in parathyroid hormone research. Clin Biochem. 1981;14(5):223-229.)
The biosynthesis of PTH and its subsequent secretion are regulated by the plasma ionized calcium (Ca2+) concentration through a complex process. An acute decrease of Ca2+ results in a marked increase of PTH mRNA, and this is followed by an increased rate of PTH synthesis and secretion. However, about 80 to 90% of the proPTH synthesized cannot be accounted for as intact PTH in cells or in the incubation medium of experimental systems. This finding led to the conclusion that most of the proPTH synthesized is quickly degraded. It was later discovered that this rate of degradation decreases when Ca2+ concentrations are low, and it increases when Ca2+ concentrations are high. A Ca2+ receptor on the surface of the parathyroid cell mediates these effects. Very specific fragments of PTH are generated during its proteolytic digestion (see Figure 1). A number of proteolytic enzymes, including cathepsins B and D, have been identified in parathyroid tissue. Cathepsin B cleaves PTH into two fragments: PTH1–36 and PTH37–84 . PTH37–84 is not further degraded; however, PTH1–36 is rapidly and progressively cleaved into di- and tripeptides. Most of the proteolysis of PTH occurs within the gland, but a number of studies con firm that PTH, once secreted, is proteolytically degraded in other tissues, especially the liver, by similar mechanisms.
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