RGD Reference Report - Aminooxy analogues of spermidine as inhibitors of spermine synthase and substrates of hepatic polyamine acetylating activity. - Rat Genome Database

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Aminooxy analogues of spermidine as inhibitors of spermine synthase and substrates of hepatic polyamine acetylating activity.

Authors: Eloranta, TO  Khomutov, AR  Khomutov, RM  Hyvonen, T 
Citation: Eloranta TO, etal., J Biochem. 1990 Oct;108(4):593-8.
RGD ID: 7242932
Pubmed: PMID:2292587   (View Abstract at PubMed)

Aminooxy analogues of spermidine, 1-aminooxy-3-N-[3-aminopropyl]- aminopropane (AP-APA) and N-[2-aminooxyethyl]-1,4-diaminobutane (AOE-PU), were tested as substrates or inhibitors of the enzymes involved in methionine and polyamine metabolism. Both compounds were good competitive inhibitors and poor substrates of spermine synthase, good substrates of cytosolic polyamine acetyltransferase, inactivators of S-adenosylmethionine decarboxylase and inhibitors of ornithine decarboxylase. AP-APA and AOE-PU showed K1-values of 1.5 and 186 microM as inhibitors of purified spermine synthase, and Km-values of 1.4 and 2.1 mM as substrates of the crude hepatic polyamine acetyltransferase activity. AP-APA was more potent than AOE-PU in crude enzyme preparations. Neither drug had any significant effect at 1 mM concentration on the activities of spermidine synthase, methionine adenosyltransferase, S-adenosylhomocysteine hydrolase, and methylthioadenosine phosphorylase. The results suggest that compounds of this type are valuable tools in unraveling the physiology of polyamines.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AHCYHumanmethionine cycle/metabolic pathway   ISOAhcy (Rattus norvegicus) RGD 
AMD1Humanmethionine cycle/metabolic pathway   ISOAmd1 (Rattus norvegicus) RGD 
AhcyRatmethionine cycle/metabolic pathway   IMP  RGD 
AhcyMousemethionine cycle/metabolic pathway   ISOAhcy (Rattus norvegicus) RGD 
Amd1Ratmethionine cycle/metabolic pathway   IMP  RGD 
Amd1Mousemethionine cycle/metabolic pathway   ISOAmd1 (Rattus norvegicus) RGD 
MAT1AHumanmethionine cycle/metabolic pathway   ISOMat1a (Rattus norvegicus) RGD 
MTAPHumanmethionine cycle/metabolic pathway   ISOMtap (Rattus norvegicus) RGD 
Mat1aRatmethionine cycle/metabolic pathway   IMP  RGD 
Mat1aMousemethionine cycle/metabolic pathway   ISOMat1a (Rattus norvegicus) RGD 
MtapRatmethionine cycle/metabolic pathway   IMP  RGD 
MtapMousemethionine cycle/metabolic pathway   ISOMtap (Rattus norvegicus) RGD 
ODC1Humanspermidine metabolic pathway  ISOOdc1 (Rattus norvegicus) RGD 
Odc1Mousespermidine metabolic pathway  ISOOdc1 (Rattus norvegicus) RGD 
Odc1Ratspermidine metabolic pathway  IMP  RGD 
SAT1Humanspermidine metabolic pathway  ISOSat1 (Rattus norvegicus) RGD 
SRMHumanspermidine metabolic pathway  ISOSrm (Rattus norvegicus) RGD 
Sat1Ratspermidine metabolic pathway  IMP  RGD 
Sat1Mousespermidine metabolic pathway  ISOSat1 (Rattus norvegicus) RGD 
SrmRatspermidine metabolic pathway  IMP  RGD 
SrmMousespermidine metabolic pathway  ISOSrm (Rattus norvegicus) RGD 
ODC1Humanspermine metabolic pathway  ISOOdc1 (Rattus norvegicus) RGD 
Odc1Ratspermine metabolic pathway  IMP  RGD 
Odc1Mousespermine metabolic pathway  ISOOdc1 (Rattus norvegicus) RGD 
SAT1Humanspermine metabolic pathway  ISOSat1 (Rattus norvegicus) RGD 
SMSHumanspermine metabolic pathway  ISOSms (Rattus norvegicus) RGD 
Sat1Mousespermine metabolic pathway  ISOSat1 (Rattus norvegicus) RGD 
Sat1Ratspermine metabolic pathway  IMP  RGD 
SmsMousespermine metabolic pathway  ISOSms (Rattus norvegicus) RGD 
SmsRatspermine metabolic pathway  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ahcy  (adenosylhomocysteinase)
Amd1  (adenosylmethionine decarboxylase 1)
Mat1a  (methionine adenosyltransferase 1A)
Mtap  (methylthioadenosine phosphorylase)
Odc1  (ornithine decarboxylase 1)
Sat1  (spermidine/spermine N1-acetyl transferase 1)
Sms  (spermine synthase)
Srm  (spermidine synthase)

Genes (Mus musculus)
Ahcy  (S-adenosylhomocysteine hydrolase)
Amd1  (S-adenosylmethionine decarboxylase 1)
Mat1a  (methionine adenosyltransferase 1A)
Mtap  (methylthioadenosine phosphorylase)
Odc1  (ornithine decarboxylase, structural 1)
Sat1  (spermidine/spermine N1-acetyl transferase 1)
Sms  (spermine synthase)
Srm  (spermidine synthase)

Genes (Homo sapiens)
AHCY  (adenosylhomocysteinase)
AMD1  (adenosylmethionine decarboxylase 1)
MAT1A  (methionine adenosyltransferase 1A)
MTAP  (methylthioadenosine phosphorylase)
ODC1  (ornithine decarboxylase 1)
SAT1  (spermidine/spermine N1-acetyltransferase 1)
SMS  (spermine synthase)
SRM  (spermidine synthase)


Additional Information