Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595044
Title: Studies on the interaction of glutamate dehydrogenase with phospholipids and with mitrochondrial membranes
Author: Nemat-Gorgani, Mohsen
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1974
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Abstract:
The object of this work was to characterise the interaction between beef liver glutamate dehydrogenase (EC 1.4.1.3), the inner mitochondrial membrane and its constituent phospholipids. Because of the similarities in the structure and properties of detergents with phospholipids, interaction of the enzyme with both types of amphiphiles was investigated. Interaction with phospholipid membranes was found to be a reversible process while detergents brought about irreversible denaturation at high concentrations. Association between the enzyme and the amphiphiles showed that the nature of the head group determines the extent of complex formation. Zwitter-ionic lysolecithin and phosphatidy1choline showed no interaction, while the anionic sodium dodecyl sulphate, phosphatidylserine and cardiolipin showed high affinity for binding to the enzyme. The apparent Ki values in the case of the two phospholipids were found to be 1 - 2 u M and 3 - 5 uM respectively in the direction of reductive aminatlon, The possibility of different conformations of the enzyme binding specifically to these charged surfaces and conformational changes brought about as a result of complex formation was investigated. The extent of binding decreased with increasing pHand ionic strength, suggesting contributions from electrostatic interactions. Evidence for hydrophobic interaction was indicated by the observation that the extent of complex formation increases with increasing temperature. Binding of the enzyme to mitochondrial membranes also indicated similar types of specificities. The enzyme showed a much higher affinity for binding to the inner surface of the inner mitochondrial membrane than to the outer surfaces of the inner and outer membranes. The extent of binding was also shown to depend on the presence of metabolites such as NADH and ADP. Binding decreased with increasing pH and ionic strength as was found for pure phospholipids. It is suggested that, in mitochondria, the reversible association between the enzyme and the inner mitochondrial membrane is controlled in a manner dependent upon the local pH, ionic strength and metabolite concentrations, and this may have important physiological significance in the control of metabolic activities of the enzyme. It is also suggested that the system exhibits the allosteric phenomenon which may be important for its regulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.595044  DOI: Not available
Keywords: QP Physiology
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