Metabolism of polyamines (Homo sapiens)

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3-56peroxisomal matrixcytosolPSMD6 PSME4 O2PXLP-K69-ODC1OAZ3 ADCH2O2PSMB5 O2PSME3 PSMC1 NASPMPSME2 CO2PSMD1 AGMAT(1-?)PTCNCO2NASPMPSMD4 SPMSMOX-326S proteasomeOAZ2 AZIN1PSMB3 PAOX:FADPSMB8 MTADPSMC5 SHFM1 dc-AdoMetPSMD5 NQO1PSMB1 SAT1NQO1 ODC:NQO1 complexAZIN1 H2O3AAPNALOAZ2 OAZ2 PSMD7 PSMA3 PSMD12 AGMPSMB11 PSMC6 H2OPXLP-K69-ODC1 PSMB10 UreaFAD PSMC3 ODC:OAZ complexSMSOAZ1 AdoMetPSMD13 PSMA5 PSMB4 PSMB7 PSMA6 OAZ1 L-ArgNASPNPSMC4 SRMCO2CoA-SHPSMB2 PSMC2 L-OrnPSMD10 NASPNPAOX PSMF1 Ac-CoAPSMD2 PSMA1 PSMD9 PutrescinePSMD14 SPNSPNPSMD11 3APALOAZ3 PXLP-K69-ODC1 H2OPSMD3 PSMB6 PSMA8 PSMB9 SPMOAZ1 OAZPXLP-K69-ODC1 AMD1(1-67)PSMA2 OAZ3 PSMA7 dc-AdoMetPSMD8 PSME1 PSMA4 AZIN1 bound OAZ:ODCcomplex1, 21


Description

Polyamines is a family of molecules (i.e. putrescine, spermine, spermidine) derived from ornithine according to a decarboxylation/condensative process. More recently, it has been demonstrated that arginine can be metabolised according to the same pathway leading to agmatine formation. Polyamines are essential for the growth, the maintenance and the function of normal cells. The complexity of their metabolism and the fact that polyamines homeostasis is tightly regulated support the idea that polyamines are essential to cell survival. Multiple abnormalities in the control of polyamines metabolism might be implicated in several pathological processes (Moinard et al., 2005). Legend for the following figure: View original pathway at Reactome.

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Reactome-Converter 
Pathway is converted from Reactome ID: 351202
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Gopinathrao, G

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Bibliography

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  1. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
  2. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  3. Moinard C, Cynober L, de Bandt JP.; ''Polyamines: metabolism and implications in human diseases.''; PubMed Europe PMC Scholia
  4. Urdiales JL, Medina MA, Sánchez-Jiménez F.; ''Polyamine metabolism revisited.''; PubMed Europe PMC Scholia
  5. Hillary RA, Pegg AE.; ''Decarboxylases involved in polyamine biosynthesis and their inactivation by nitric oxide.''; PubMed Europe PMC Scholia
  6. Zhu MY, Iyo A, Piletz JE, Regunathan S.; ''Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115017view16:55, 25 January 2021ReactomeTeamReactome version 75
113462view11:53, 2 November 2020ReactomeTeamReactome version 74
112662view16:04, 9 October 2020ReactomeTeamReactome version 73
101578view11:44, 1 November 2018ReactomeTeamreactome version 66
101114view21:28, 31 October 2018ReactomeTeamreactome version 65
100642view20:02, 31 October 2018ReactomeTeamreactome version 64
100192view16:47, 31 October 2018ReactomeTeamreactome version 63
99742view15:13, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99308view12:46, 31 October 2018ReactomeTeamreactome version 62
93775view13:35, 16 August 2017ReactomeTeamreactome version 61
93302view11:19, 9 August 2017ReactomeTeamreactome version 61
87888view12:26, 25 July 2016RyanmillerOntology Term : 'polyamine metabolic pathway' added !
87887view12:25, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86386view09:16, 11 July 2016ReactomeTeamreactome version 56
83445view12:25, 18 November 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
3AAPNALMetaboliteCHEBI:30322 (ChEBI)
3APALMetaboliteCHEBI:18090 (ChEBI)
ADCProteinQ96A70 (Uniprot-TrEMBL)
AGMAT(1-?)ProteinQ9BSE5 (Uniprot-TrEMBL)
AGMMetaboliteCHEBI:17431 (ChEBI)
AMD1(1-67)ProteinP17707 (Uniprot-TrEMBL)
AZIN1 ProteinO14977 (Uniprot-TrEMBL)
AZIN1 bound OAZ:ODC complexComplexR-HSA-353105 (Reactome)
AZIN1ProteinO14977 (Uniprot-TrEMBL)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
FAD MetaboliteCHEBI:16238 (ChEBI)
H2O2MetaboliteCHEBI:16240 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
L-ArgMetaboliteCHEBI:32682 (ChEBI)
L-OrnMetaboliteCHEBI:15729 (ChEBI)
MTADMetaboliteCHEBI:17509 (ChEBI)
NASPMMetaboliteCHEBI:17927 (ChEBI)
NASPNMetaboliteCHEBI:17312 (ChEBI)
NQO1 ProteinP15559 (Uniprot-TrEMBL)
NQO1ProteinP15559 (Uniprot-TrEMBL)
O2MetaboliteCHEBI:15379 (ChEBI)
OAZ1 ProteinP54368 (Uniprot-TrEMBL)
OAZ2 ProteinO95190 (Uniprot-TrEMBL)
OAZ3 ProteinQ9UMX2 (Uniprot-TrEMBL)
OAZComplexR-HSA-350592 (Reactome)
ODC:NQO1 complexComplexR-HSA-353103 (Reactome)
ODC:OAZ complexComplexR-HSA-353118 (Reactome)
PAOX ProteinQ6QHF9 (Uniprot-TrEMBL)
PAOX:FADComplexR-HSA-141346 (Reactome)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
PTCNMetaboliteCHEBI:17148 (ChEBI)
PXLP-K69-ODC1 ProteinP11926 (Uniprot-TrEMBL)
PXLP-K69-ODC1ProteinP11926 (Uniprot-TrEMBL)
PutrescineMetaboliteCHEBI:17148 (ChEBI)
SAT1ProteinP21673 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SMOX-3ProteinQ9NWM0-3 (Uniprot-TrEMBL)
SMSProteinP52788 (Uniprot-TrEMBL)
SPMMetaboliteCHEBI:16610 (ChEBI)
SPNMetaboliteCHEBI:15746 (ChEBI)
SRMProteinP19623 (Uniprot-TrEMBL)
UreaMetaboliteCHEBI:16199 (ChEBI)
dc-AdoMetMetaboliteCHEBI:15625 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-353125 (Reactome)
3AAPNALArrowR-HSA-141348 (Reactome)
3AAPNALArrowR-HSA-141351 (Reactome)
3APALArrowR-HSA-141341 (Reactome)
ADCmim-catalysisR-HSA-350598 (Reactome)
AGMAT(1-?)mim-catalysisR-HSA-350604 (Reactome)
AGMArrowR-HSA-350598 (Reactome)
AGMR-HSA-350604 (Reactome)
AMD1(1-67)mim-catalysisR-HSA-351222 (Reactome)
AZIN1 bound OAZ:ODC complexArrowR-HSA-350600 (Reactome)
AZIN1R-HSA-350600 (Reactome)
Ac-CoAR-HSA-351207 (Reactome)
Ac-CoAR-HSA-351208 (Reactome)
AdoMetR-HSA-351222 (Reactome)
CO2ArrowR-HSA-350598 (Reactome)
CO2ArrowR-HSA-351222 (Reactome)
CO2ArrowR-HSA-70692 (Reactome)
CoA-SHArrowR-HSA-351207 (Reactome)
CoA-SHArrowR-HSA-351208 (Reactome)
H2O2ArrowR-HSA-141341 (Reactome)
H2O2ArrowR-HSA-141348 (Reactome)
H2O2ArrowR-HSA-141351 (Reactome)
H2OR-HSA-141341 (Reactome)
H2OR-HSA-141348 (Reactome)
H2OR-HSA-141351 (Reactome)
H2OR-HSA-350604 (Reactome)
L-ArgR-HSA-350598 (Reactome)
L-OrnR-HSA-70692 (Reactome)
MTADArrowR-HSA-351210 (Reactome)
MTADArrowR-HSA-351215 (Reactome)
NASPMArrowR-HSA-351201 (Reactome)
NASPMArrowR-HSA-351208 (Reactome)
NASPMR-HSA-141348 (Reactome)
NASPMR-HSA-351201 (Reactome)
NASPNArrowR-HSA-351207 (Reactome)
NASPNArrowR-HSA-351229 (Reactome)
NASPNR-HSA-141351 (Reactome)
NASPNR-HSA-351229 (Reactome)
NQO1R-HSA-350578 (Reactome)
O2R-HSA-141341 (Reactome)
O2R-HSA-141348 (Reactome)
O2R-HSA-141351 (Reactome)
OAZArrowR-HSA-353125 (Reactome)
OAZR-HSA-350567 (Reactome)
ODC:NQO1 complexArrowR-HSA-350578 (Reactome)
ODC:OAZ complexArrowR-HSA-350567 (Reactome)
ODC:OAZ complexR-HSA-350600 (Reactome)
ODC:OAZ complexR-HSA-353125 (Reactome)
PAOX:FADmim-catalysisR-HSA-141348 (Reactome)
PAOX:FADmim-catalysisR-HSA-141351 (Reactome)
PTCNArrowR-HSA-141348 (Reactome)
PXLP-K69-ODC1R-HSA-350567 (Reactome)
PXLP-K69-ODC1R-HSA-350578 (Reactome)
PXLP-K69-ODC1mim-catalysisR-HSA-70692 (Reactome)
PutrescineArrowR-HSA-350604 (Reactome)
PutrescineArrowR-HSA-70692 (Reactome)
PutrescineR-HSA-351215 (Reactome)
R-HSA-141341 (Reactome) Spermine oxidase (SMOX, PAOh1, SMO) is a polyamine oxidase flavoenzyme that catalyses the oxidation of spermine (SPN) to spermidine (SPM). It plays an important role in the regulation of endogenous polyamine intracellular concentration. Five different isozymes are produced by alternative splicing with isozyme 3 being the major isoform and possessing the highest affinity for spermine. It is highly inducible by specific antitumor polyamine analogues (Wang et al. 2001).
R-HSA-141348 (Reactome) Acetylated spermidine (NASPM) is oxidised by the flavoenzyme polyamine oxidase (PAOX, with FAD as cofactor) to produce putrescine (PTCN). PAOX is involved in the back-conversion of polyamines and thus the regulation of their intracellular concentrations (Vujcic et al. 2003).
R-HSA-141351 (Reactome) Acetylated spermine (NASPN) is oxidised by the flavoenzyme polyamine oxidase (PAOX, woth FAD as cofactor) to produce spermidine (SPM). PAOX is involved in the back-conversion of polyamines and thus the regulation of their intracellular concentrations (Vujcic et al. 2003).
R-HSA-350567 (Reactome) Antizyme is a non-competitive inhibitor of ODC that is synthesized in response to an increase in polyamine concentration. Tight binding of the antizyme to the ODC monomer forming a heterodimer prevents enzymatic activity. The region of antizyme interacting with ODC is contained in a section involving residues 106–212 in the COOH-terminal half of the antizyme molecule. The induction of antizyme thus leads to a loss of active ODC protein (Pegg, 2006 and references cited in that review).

R-HSA-350578 (Reactome) A novel pathway has been described for ODC degradation during oxidative stress, which is regulated by NAD(P)H quinone oxidoreductase (NQO1). In this pathway, the 20S proteasome has been shown to degrade unfolded ODC monomers. This event does not require the COOH-terminal domain. NQO1 binds to ODC and stabilizes it. If this interaction is disrupted with dicoumarol, it sensitizes ODC monomers to degradation by the 20S proteasome independent of both antizyme and ubiquitin. The details of the role of this pathway remains to be determined, but it could be involved in the nascent ODC chain turnover.
R-HSA-350598 (Reactome) Agmatine is polyamine formed by decarboxylation of L-arginine by arginine decarboxylase (ADC). Human ADC is a 460-amino acid protein that shows about 48% identity to mammalian ornithine decarboxylase (ODC) but has no ODC activity.
R-HSA-350600 (Reactome) Antizyme inhibitor blocks the effects of antizyme on ODC. It has substantial similarity to ODC itself but has no ODC activity. It binds to antizyme more tightly than ODC displacing ODC from the antizyme-ODC complex. Recent studies have shown that antizyme inhibitor is able to disrupt the interaction between all forms of mammalian antizyme and ODC (Murakami et al., 1996, Nilsson et al., 2000, Mangold and Leberer, 2005).
R-HSA-350604 (Reactome) As it hydrolyzes a guanidino group within agmatine and also contains signature amino acid residues that act as ligand binding sites for the potential Mn(++) cofactor, agmatinase is classified as a member of the arginase superfamily (Morris, 2003).
R-HSA-351201 (Reactome) The N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells. The kinetics of this enzyme has been already elucidated (Hedge et al. 2007).
R-HSA-351207 (Reactome) Spermidine/spermine N1-acetyltransferase (Spd/Spm acetyltransferase) is the rate-limiting enzyme in the catabolism of polyamines. Defects in SAT1 may be the cause of keratosis follicularis spinulosa decalvans (KFSD).
R-HSA-351208 (Reactome) Spermidine/spermine N1-acetyltransferase (Spd/Spm acetyltransferase) is the rate-limiting enzyme in the catabolism of polyamines. Defects in SAT1 may be the cause of keratosis follicularis spinulosa decalvans (KFSD).
R-HSA-351210 (Reactome) The protein encoded by this gene belongs to the spermidine/spermine synthases family. This gene encodes an ubiquitous enzyme of polyamine metabolism. Defects in SMS are the cause of Snyder-Robinson syndrome (SRS).
R-HSA-351215 (Reactome) Spermidine synthase is one of four enzymes in the polyamine-biosynthetic pathway and carries out the final step of spermidine biosynthesis. This enzyme catalyzes the conversion of putrescine to spermidine using decarboxylated S-adenosylmethionine as the cofactor.
R-HSA-351222 (Reactome) S-Adenosylmethionine decarboxylase belongs to a small class of amino acid decarboxylases that use a covalently bound pyruvate as a prosthetic group. It is an essential enzyme for polyamine biosynthesis and provides an important target for the design of anti-parasitic and cancer chemotherapeutic agents. It catalyzes the formation of the aminopropyl group donor in the biosynthesis of the polyamines spermidine and spermine. These pyruvoyl-dependent decarboxylases also form amines such as histamine, decarboxylated S-adenosylmethionine, phosphatidylethanolamine (a component of membrane phospholipids), and -alanine (a precursor of coenzyme A), which are all of critical importance in cellular physiology and provide important targets for drug design.
R-HSA-351229 (Reactome) The N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells. The kinetics of this enzyme has been already elucidated (Hedge et al. 2007).
R-HSA-353125 (Reactome) The rapid turnover of ODC is brought about by the 26S proteasome. Proteolytic processing of ODC is highly unusual in that ubiquitination is not required for this degradation. Instead, a non-covalent association with antizyme directs ODC to the proteasome. Antizyme increases the degradation of ODC by enhancing its interaction with the proteasome (Pegg, 2006).
R-HSA-70692 (Reactome) L-ornithine is converted into putrescine by ODC holoenzyme complex.Putrescine is subsequent used for polyamine synthesis.
SAT1mim-catalysisR-HSA-351207 (Reactome)
SAT1mim-catalysisR-HSA-351208 (Reactome)
SMOX-3mim-catalysisR-HSA-141341 (Reactome)
SMSmim-catalysisR-HSA-351210 (Reactome)
SPMArrowR-HSA-141341 (Reactome)
SPMArrowR-HSA-141351 (Reactome)
SPMArrowR-HSA-351215 (Reactome)
SPMR-HSA-351208 (Reactome)
SPMR-HSA-351210 (Reactome)
SPNArrowR-HSA-351210 (Reactome)
SPNR-HSA-141341 (Reactome)
SPNR-HSA-351207 (Reactome)
SRMmim-catalysisR-HSA-351215 (Reactome)
UreaArrowR-HSA-350604 (Reactome)
dc-AdoMetArrowR-HSA-351222 (Reactome)
dc-AdoMetR-HSA-351210 (Reactome)
dc-AdoMetR-HSA-351215 (Reactome)
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