Cellular Mechanisms of Peptide Processing: Focus on α-Amidation

  • Richard E. Mains
  • Victor May
  • Edward I. Cullen
  • Betty A. Eipper
Part of the Biochemical Endocrinology book series (BIOEND)


It is now well accepted that a vast array of peptides play essential roles in intercellular communication in both the nervous and endocrine systems. Many neurons contain both a classical neurotransmitter and a peptide (Krieger, 1983; Jones & Hendry, 1986). While we know a great deal about the control mechanisms affecting neuronal synthesis, storage and secretion of classical neurotransmitters such as the catecholamines and acetylcholine, we know relatively little about the precise way in which neuronal peptides are regulated. Our lack of knowledge concerning the mechanisms by which the synthesis, storage and secretion of bioactive peptides can be manipulated stems in large part from the relative lack of knowledge about the specific enzymes involved in converting inactive peptide precursors into their final bioactive products.


Tyrosine Hydroxylase Secretory Granule Amidated Peptide Classical Neurotransmitter Aromatic Amino Acid Decarboxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ando S, Murthy ASN, Eipper BA, Chaiken IM 1987 Effect of neurophysin on enzymatic maturation on oxytocin from its precursor. J Biol Chem 262, in press.Google Scholar
  2. Bradbury AF, Finnie MDA, Smyth DG 1982 Mechanism of G-terminal amide formation by pituitary enzymes. Nature 298:686–688.PubMedCrossRefGoogle Scholar
  3. Bradbury AF, Smyth DG 1985 C-terminal amide formation in peptide hormones. In: “Biogenetics of Neurohormonal Peptides”, Hakanson R & Thoreil J (eds), Academic Press, New York, pp 171–186.Google Scholar
  4. Campbell DG, Hardie DG, Vulliet PR 1986 Identification of four phosphorylation sites in the N-terminal region of tyrosine hydroxylase. J Biol Chem 261:10489–10492.PubMedGoogle Scholar
  5. Carlson A 1987 Perspectives on the discovery of central monoaminergic neurotransmission. Annu Rev Neurosci 10:19–40.CrossRefGoogle Scholar
  6. Cooper JR, Bloom FE, Roth RH 1986 The “Biochemical Basis of Neuropharmacology”. Oxford University Press, New York.Google Scholar
  7. Dickerson IM, Dixon JE, Mains RE 1987 Transfected human neuropeptide Y cDNA expression in mouse pituitary cells. J Biol Chem 262, in press.Google Scholar
  8. Edelman AM, Blumenthal DK, Krebs EG 1987 Protein serine/threonine kinases. Annu Rev Biochem 56:567–613.PubMedCrossRefGoogle Scholar
  9. Eipper BA, Mains RE, Glembotski CC 1983 Identification in pituitary tissue of a peptide α-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. Proc Natl Acad Sci USA 80:5144–5148.PubMedCrossRefGoogle Scholar
  10. Eipper BA, Myers AC, Mains RE 1985 Peptidyl-glycine α-amidation activity in tissues and serum of the adult rat. Endocrinology 116:2497–2504.PubMedCrossRefGoogle Scholar
  11. Eipper BA, Park LP, Dickerson IM, Keutmann HT, Thiele EA, Rodriguez H, Schofield PR, Mains RE 1987 Structure of the precursor to an enzyme mediating C00H-terminal amidation in peptide biosynthesis. Mol Endocrinol 1, in press.Google Scholar
  12. Fricker LD 1988 Carboxypeptidase E. Annu Rev Physiol 50, in press.Google Scholar
  13. Fricker LD, Evans CJ, Esch FS, Herbert E 1986 Cloning and sequence analysis of cDNA for bovine carboxypeptidase E. Nature 323:461–464.PubMedCrossRefGoogle Scholar
  14. Jones EG, Hendry SHC 1986 Colocalization of GABA and neuropeptides in neocortical neurons. Trends Neurosci 9:71–76.CrossRefGoogle Scholar
  15. Kizer JS, Bateman RC Jr, Miller CR, Humm J, Busby WH Jr, Youngblood WW 1986 Purification and characterization of a peptidyl-glycine monooxygenase from porcine pituitary. Endocrinology 118:2262–2267.PubMedCrossRefGoogle Scholar
  16. Krieger DT 1983 Brain peptides: what, where, and why? Science 222:975–985.PubMedCrossRefGoogle Scholar
  17. Kyte J, Doolittle RF 1982 A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132.PubMedCrossRefGoogle Scholar
  18. Mains RE, Eipper BA 1984 Secretion and regulation of two biosynthetie enzyme activities, PAM and CPE, by mouse pituitary corticotropic tumor cells. Endocrinology 115:1683–1690.PubMedCrossRefGoogle Scholar
  19. Mains RE, Glembotski CC, Eipper BA 1984 Peptide α-amidation activity in mouse anterior pituitary AtT-20 cell granules; properties and secretion. Endocrinology 114:1522–1530.PubMedCrossRefGoogle Scholar
  20. May V, Cullen EI, Braas KM, Eipper BA 1988 Membrane-associated forms of peptidyl-glycine α-amidating mono oxygenase activity in pituitary: tissue specificity. Submitted.Google Scholar
  21. Mehta NM, Gilligan JP, Jones BN, Tamburini PP, Birnbaum RS, Roos BA, Bertelsen AH 1987 Purification and characterization of an amidating enzyme involved in peptide hormone processing. Endocrinology 120:196a.Google Scholar
  22. Mizuno K, Sakata J, Kojima M, Kangawa K, Matsuo H 1986 Peptide G-terminal α-amidating enzyme purified to homogeneity from Xenopus laevis skin. Biochem Biophys Res Commun 137:984–991.PubMedCrossRefGoogle Scholar
  23. Mollay C., Wichta J, Kreil G 1986 Detection and partial characterization of an amidating enzyme in skin secretion of Xenopus laevis. FEBS Lett 202:251–254.CrossRefGoogle Scholar
  24. Moore RY, Bloom FE 1979 Central catecholamine neuron systems. Annu Rev Neurosci 2:113–168.PubMedCrossRefGoogle Scholar
  25. Murthy ASN, Keutmann HT, Eipper BA 1987 Further characterization of peptidyl-glycine α-amidating monooxygenase from bovine neurointermediate pituitary. Mol Endocrinol 1:290–299.PubMedCrossRefGoogle Scholar
  26. Murthy ASN, Mains RE, Eipper BA 1986 Purification and characterization of peptidyl-glycine α-amidating monooxygenase from bovine neurointermediate pituitary. J Biol Chem 261:1815–1822.PubMedGoogle Scholar
  27. Park LP, Thiele EA, Dickerson IM, Mains RE, Eipper BA 1987 Cloning of cDNA encoding bovine PAM. In: “Highlights on Endocrinology”, Christiansen C & Riis BJ (eds) Norhaven Bogtrykkeri, Copenhagen, pp 133–140.Google Scholar
  28. Pocotte SL, Holz RW, Ueda T 1986 Cholinergic receptor-mediated phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells. J Neurochem 46:610–622.PubMedCrossRefGoogle Scholar
  29. Sakata J, Mizuno K, Matsuo H 1986 Tissue distribution and characterization of peptide C-terminal α-amidating activity in rat. Biochem Biophys Res Commun 140:230–236.PubMedCrossRefGoogle Scholar
  30. Sato SM, Mains RE 1988 Plasticity in the ACTH-related peptides produced by primary cultures of neonatal rat pituitary. Endocrinology 122, in press.Google Scholar
  31. Seguin C., Hamer DH 1987 Regulation in vitro of metallothionein gene binding factors. Science 235:1383–1387.PubMedCrossRefGoogle Scholar
  32. Sigel H (ed) 1981 “Metal Ions in Biological Systems”. Marcel Dekker, Inc., New York, vol 13.Google Scholar
  33. Tramu G, Pillez A, Leonardelli J 1978 An efficient method of antibody elution for the successive or simultaneous localization of two antigens by immunocytochemistry. J Histochem Cytochem 26:322–324.PubMedCrossRefGoogle Scholar
  34. van der Eb AJ, Graham FL 1980 Assay of transforming activity of tumor virus DNA. Methods Enzymol 65:826–839.PubMedCrossRefGoogle Scholar
  35. von Heijne G 1981 Membrane proteins: the amino acid composition of membrane-penetrating segments. Eur J Biochem 120:275–278.CrossRefGoogle Scholar
  36. von Heijne G 1985 Signal sequences: the limits of variation. J Mol Biol 184:99–105.CrossRefGoogle Scholar
  37. Walter P, Lingappa VR 1986 Mechanism of protein translocation across the endoplasmic reticulum membrane. Annu Rev Cell Biol 2:499–516.PubMedCrossRefGoogle Scholar
  38. Wand GS, Ney RL, Baylin S, Eipper BA, Mains RE 1985 Characterization of a peptide α-amidation activity in human plasma and tissues. Metabolism 34:1044–1052.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Richard E. Mains
    • 1
  • Victor May
    • 1
  • Edward I. Cullen
    • 1
  • Betty A. Eipper
    • 1
  1. 1.Department of NeuroscienceThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations