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Gene Review

Pam  -  peptidylglycine alpha-amidating monooxygenase

Rattus norvegicus

Synonyms: PAM, Peptidyl-glycine alpha-amidating monooxygenase
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Disease relevance of Pam


Psychiatry related information on Pam


High impact information on Pam

  • Genes coding for the neuropeptide hormone pituitary adenylate cyclase activating polypeptide (PACAP) and the enzyme that processes PACAP's precursor to the mature form, peptidylglycine alpha-amidating monooxygenase, were upregulated by inositol depletion [7].
  • Chronic treatment of ovariectomized rats with 17beta-estradiol decreased PAM mRNA levels to values comparable with those found in intact rats at proestrus [8].
  • In the present study, high levels of peptidylglycine alpha-amidating monooxygenase (PAM), which catalyzes the two-step formation of bioactive alpha-amidated peptides from their glycine-extended precursors, have been found in the uterus [8].
  • The levels of PAM transcripts changed markedly during the estrous cycle, reaching the highest levels at metestrus [8].
  • These results demonstrate the presence of high levels of PAM in the uterus and indicate that estrogens are involved in regulating the expression of the enzyme in this tissue [8].

Chemical compound and disease context of Pam


Biological context of Pam


Anatomical context of Pam

  • We demonstrate here by subcellular fractionation and biochemical analyses that PAM co-localizes with pro-ANP in secretory granules, where together they constitute the two most abundant membrane-associated proteins, accounting for approximately 95% of the total granular membrane protein [9].
  • Additionally, we demonstrate that while pro-ANP is readily found in the soluble contents of the granule lumen, significant amounts remain tightly associated with the membranes even after vigorous washing and estimate the molar ratio of pro-ANP to PAM to be approximately 30:1 in the membrane fraction [9].
  • We have isolated and sequenced cDNAs representing the two major classes of PAM mRNA in the adult rat heart atrium [10].
  • In the heart and central nervous system, PAM mRNAs both containing and lacking optional Exon A were prevalent and almost all of the PAM mRNAs detected contained optional Exon B [12].
  • Biotinylation studies established that the appearance of integral membrane PAM at the plasma membrane was stimulated along with hormone secretion [13].

Associations of Pam with chemical compounds

  • ANP is not amidated by PAM, but rather is processed to its active form (amino acids 99-126) by the proteolytic cleavage of pro-ANP [9].
  • Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC catalyzes the conversion of a variety of glycine-extended peptides into biologically active alpha-amidated product peptides in a reaction dependent on copper, ascorbate, and molecular oxygen [10].
  • We examined the turnover of peptidylglycine alpha-amidating monooxygenase (PAM), a membrane enzyme involved in the final maturation of many peptides, and VAMP2, a vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) [13].
  • We report here that thiorphan and tiopronin are substrates for PAM, exhibiting relatively low K(M,app) and V(MAX,app) values [14].
  • Progesterone was without effect on PAM mRNA levels, indicating that the effect was specific for estradiol [8].

Other interactions of Pam


Analytical, diagnostic and therapeutic context of Pam


  1. Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase. Chew, G.H., Galloway, L.C., McIntyre, N.R., Schroder, L.A., Richards, K.M., Miller, S.A., Wright, D.W., Merkler, D.J. FEBS Lett. (2005) [Pubmed]
  2. Suppression of substance P biosynthesis in sensory neurons of dorsal root ganglion by prodrug esters of potent peptidylglycine alpha-amidating monooxygenase inhibitors. Jeng, A.Y., Fujimoto, R.A., Chou, M., Tan, J., Erion, M.D. J. Biol. Chem. (1997) [Pubmed]
  3. Effect of thyroid hormones on peptidylglycine alpha-amidating monooxygenase gene expression in anterior pituitary gland: transcriptional studies and messenger ribonucleic acid stability. Fraboulet, S., Boudouresque, F., Delfino, C., Fina, F., Oliver, C., Ouafik, L. Endocrinology (1996) [Pubmed]
  4. Gut endotoxin restriction improves postoperative hemodynamics in the bile duct-ligated rat. Houdijk, A.P., van Lambalgen, A.A., Thijs, L.G., van Leeuwen, P.A. Shock (1998) [Pubmed]
  5. Differences in the ways sympathetic neurons and endocrine cells process, store, and secrete exogenous neuropeptides and peptide-processing enzymes. Marx, R., El Meskini, R., Johns, D.C., Mains, R.E. J. Neurosci. (1999) [Pubmed]
  6. Plasticity in hippocampal peptidergic systems induced by repeated electroconvulsive shock. Ma, X.M., Mains, R.E., Eipper, B.A. Neuropsychopharmacology (2002) [Pubmed]
  7. Regulation of gene expression by lithium and depletion of inositol in slices of adult rat cortex. Brandish, P.E., Su, M., Holder, D.J., Hodor, P., Szumiloski, J., Kleinhanz, R.R., Forbes, J.E., McWhorter, M.E., Duenwald, S.J., Parrish, M.L., Na, S., Liu, Y., Phillips, R.L., Renger, J.J., Sankaranarayanan, S., Simon, A.J., Scolnick, E.M. Neuron (2005) [Pubmed]
  8. Evidence of high expression of peptidylglycine alpha-amidating monooxygenase in the rat uterus: estrogen regulation. El Meskini, R., Delfino, C., Boudouresque, F., Oliver, C., Martin, P.M., Ouafik L'H, n.u.l.l. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Peptidylglycine-alpha-amidating monooxygenase and pro-atrial natriuretic peptide constitute the major membrane-associated proteins of rat atrial secretory granules. O'Donnell, P.J., Driscoll, W.J., Bäck, N., Muth, E., Mueller, G.P. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  10. Alternative mRNA splicing generates multiple forms of peptidyl-glycine alpha-amidating monooxygenase in rat atrium. Stoffers, D.A., Green, C.B., Eipper, B.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. Alternative splicing and endoproteolytic processing generate tissue-specific forms of pituitary peptidylglycine alpha-amidating monooxygenase (PAM). Eipper, B.A., Green, C.B., Campbell, T.A., Stoffers, D.A., Keutmann, H.T., Mains, R.E., Ouafik, L. J. Biol. Chem. (1992) [Pubmed]
  12. Characterization of novel mRNAs encoding enzymes involved in peptide alpha-amidation. Stoffers, D.A., Ouafik, L., Eipper, B.A. J. Biol. Chem. (1991) [Pubmed]
  13. Retrieval and reuse of pituitary secretory granule proteins. Ferraro, F., Eipper, B.A., Mains, R.E. J. Biol. Chem. (2005) [Pubmed]
  14. Thiorphan, tiopronin, and related analogs as substrates and inhibitors of peptidylglycine alpha-amidating monooxygenase (PAM). McIntyre, N.R., Lowe, E.W., Chew, G.H., Owen, T.C., Merkler, D.J. FEBS Lett. (2006) [Pubmed]
  15. Regulation of thyrotropin-releasing hormone in the posterior pituitary. Rondeel, J.M., Klootwijk, W., Linkels, E., van Haasteren, G.A., de Greef, W.J., Visser, T.J. Neuroendocrinology (1995) [Pubmed]
  16. Expression of catecholamine-synthesizing enzymes, peptidylglycine alpha-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine. Jahng, J.W., Houpt, T.A., Joh, T.H., Wessel, T.C. J. Mol. Neurosci. (1997) [Pubmed]
  17. Peptidylglycine alpha-amidating monooxygenase activity and TRH and CRF biosynthesis. Role of copper. Giraud, P., Maltèse, J.Y., Boudouresque, F., Salers, P., Ouafik, L., Renard, M., Pelen, F., Oliver, C. Biological trace element research. (1992) [Pubmed]
  18. Alterations of rat brain peptidylglycine alpha-amidating monooxygenase and other cuproenzyme activities following perinatal copper deficiency. Prohaska, J.R., Bailey, W.R. Proc. Soc. Exp. Biol. Med. (1995) [Pubmed]
  19. An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. Penzes, P., Johnson, R.C., Alam, M.R., Kambampati, V., Mains, R.E., Eipper, B.A. J. Biol. Chem. (2000) [Pubmed]
  20. Membrane-associated peptidylglycine alpha-amidating monooxygenase in the heart. Eipper, B.A., May, V., Braas, K.M. J. Biol. Chem. (1988) [Pubmed]
  21. Developmental regulation of peptidylglycine alpha-amidating monooxygenase (PAM) in rat heart atrium and ventricle. Tissue-specific changes in distribution of PAM activity, mRNA levels, and protein forms. Ouafik, L., May, V., Keutmann, H.T., Eipper, B.A. J. Biol. Chem. (1989) [Pubmed]
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