RGD Reference Report - Metabolism of threo-beta-fluoroaspartate by H4 cells. Inhibition of adenylosuccinate lyase by fluoro analogs of its substrates. - Rat Genome Database

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Metabolism of threo-beta-fluoroaspartate by H4 cells. Inhibition of adenylosuccinate lyase by fluoro analogs of its substrates.

Authors: Casey, PJ  Abeles, RH  Lowenstein, JM 
Citation: Casey PJ, etal., J Biol Chem. 1986 Oct 15;261(29):13637-42.
RGD ID: 5135303
Pubmed: PMID:3759987   (View Abstract at PubMed)

DL-threo-beta-Fluoroaspartate is a substrate for the two enzymes in de novo purine biosynthesis that use aspartate, namely 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) synthetase and adenylosuccinate synthetase. With both enzymes, Vmax with threo-beta-fluoroaspartate is about 50% of that observed with aspartate. The products of the two enzyme reactions, threo-beta-fluoro-SAICAR and threo-beta-fluoroadenylosuccinate, are inhibitors of adenylosuccinate lyase purified from rat skeletal muscle. In 20 mM phosphate buffer, pH 7.4, the KI values for threo-beta-fluoro-SAICAR are 5 and 3 microM and for threo-beta-fluoroadenylosuccinate are 3 and 1 microM, in the SAICAR and adenylosuccinate cleavage reactions, respectively. In 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, pH 7.4, the KI values for threo-beta-fluoro-SAICAR are approximately 0.14 and 0.03 microM and for threo-beta-fluoroadenylosuccinate are approximately 0.05 and 0.015 microM, in the same two reactions, respectively. These KI values are one-half to one-hundredth of the Km values for SAICAR and adenylosuccinate, the two substrates of adenylosuccinate lyase. After an 8-h incubation with 45 microM threo-beta-fluoroaspartate, H4 cells contain 200-300 microM threo-beta-fluoro-SAICAR and 60-90 microM threo-beta-fluoroadenylosuccinate. These concentrations of fluoro analogs are sufficient to substantially inhibit adenylosuccinate lyase and hence the de novo synthesis of purines in H4 cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AdslRatAMP biosynthetic process  IDA  RGD 
Adss1Rataspartate metabolic process  IDA  RGD 
Adss1RatIMP metabolic process  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AdslRat(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity  IDA  RGD 
Adss1Ratadenylosuccinate synthase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adsl  (adenylosuccinate lyase)
Adss1  (adenylosuccinate synthase 1)

Objects referenced in this article
Gene Adss2 adenylosuccinate synthase 2 Rattus norvegicus

Additional Information