Studies on the phosphonic acid analogues of gamma-aminobutyric acid and L-glutamic acid.

  • P. D. Turner

Student thesis: Doctoral ThesisPhD


The phosphonate compounds 3-aminopropylphosphonate (APP) and 2-amino-4-phosphonobutyrate were assessed as analogues of gamma-aminobutyrate (GABA) and L-glutamate, respectively, in a range of systems involved in the neurotransmitter roles of GABA and L-glutamate in mammalian brain. These systems included sites for post-synaptic binding and high-affinity uptake and a number of enzymes. APP was shown to inhibit the binding of GABA to its post-synaptic receptor, having an IC50 value of 7.08 mM and, at 2.0 mM, to have no effect on the high-affinity uptake of GABA. APP inhibited GABA:2-oxoglutarate aminotransferase (E.C. by 58% at 25 mM and was a substrate for this enzyme (17% of the rate obtained with 25 mM-GABA). APB (at 1.0 mM) was shown not to interact with the high affinity uptake system for L-glutamate and had no effect on L-glutamate:oxaloacetate aminotransferase (E.C. at 25.0 mM. At 10.0 mM APB inhibited L-alanine:2-oxoglutarate aminotransferase (E.C. by 11% and L-glutamate decarboxylase (E.C. by 29% but had no effect on L-glutamine synthetase (E.C. APB inhibited L-glutamate dehydrogenase (E.C. and kinetic analysis showed that three inhibition mechanisms were possible all of which involved binding by APB to both the L-glutamate and NAD+ binding sites. True Ki values were determined and were between 0.1 and 4.0 mM.
Date of Award1980
Original languageEnglish
Awarding Institution
  • University of Bath

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