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Title: Fatty acids and the regulation of pyruvate dehydrogenase interconversion
Author: Stewart, Melanie Ann
ISNI:       0000 0001 3485 1442
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1997
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This thesis presents evidence for a novel mechanism of regulation of pyruvate dehydrogenase (PDH) kinase by fatty acids and also results of a study of muscle triacylglycerol concentration. In animals regulation of PDH complex activity is central to the selection of respiratory fuels and to the conservation of glucose during carbohydrate deprivation. The principal means of regulation of PDH complex is interconversion of phosphorylated (inactive) and dephosphorylated (active) forms effected by PDH kinase and PDH phosphatase. Earlier in vitro studies by others had identified both shorter term (min) and longer term (hours) mechanisms of activation of PDH kinase by fatty acid. In the present study PDH kinase activity (as measured by rates of ATP-dependent inactivation of PDH complex in extracts) was shown to be increased when rat heart mitochondria were incubated with palmitoyl-L-carnitine [PC] (and other CoA utilising respiratory substrates). The activation of PDH kinase persisted through removal of respiratory substrate following incubation with CCCP. A comparable effect of PC was also demonstrable in heart mitochondria from 48h-starved rats (i.e. the mechanism may be distinct from that which increases PDH kinase activity in starvation). Rates of ATP-dependent inactivation of PDH complex were also increased when extracts of rat heart mitochondria were incubated with palmitoyl-CoA (PCoA); the increase was comparable with that seen on incubation of intact mitochondria with PC. The PC effect in intact mitochondria and the PCoA effect in mitochondrial extracts may not be identical as PCoA further increased PDH kinase activity in extracts from mitochondria incubated with PC. Rates of incorporation of 32P from [γ-32
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pyruvates ; Dehydrogenases ; Secretion ; Regulation ; Fatty acids ; Enzymology