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Title: Multiple forms of ATP citrate lyase from rat liver and brain
Author: Wilson, Anne Patricia
Awarding Body: University of London
Current Institution: Royal Holloway, University of London
Date of Award: 1984
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ATP citrate lyase (ATP citrate (pro-3S)-lyase EC, an enzyme which produces cytoplasmic acetyl CoA for biosynthetic pathways, is shown to exist in multiple forms in rat liver and brain. The enzyme in crude supernatants of both tissues has been separated into two fractions by ion-exchange chromatography. The first peak of activity was eluted immediately, without retention, whilst the remaining activity was adsorbed on the column and was eluted by a salt gradient. Whereas only a minor proportion of the total liver activity (15 - 20%) was present in the non-retained, basic peak, it contained 40% of the brain enzyme. Gel filtration of crude liver extracts revealed the presence of a high molecular weight component of ATP citrate lyase, comprising 10% of the total activity, rin addition to the tetrameric enzyme. This high molecular weight form was absent from brain supernatants. An estimated molecular weight of 410,000 was obtained for the tetramer using a calibrated gel filtration column. Rechromatography experiments with the non-retained, basic form and the high molecular weight component, from liver, indicated that both are unstable. High-speed centrifugation of liver homogenates showed that the minor peak of activity from ion-exchange is not the same as the high molecular weight activity since removal of the latter did not result in loss of the non-retained peak. No evidence could be found for an association of ATP citrate lyase with the enzymes fatty acid synthetase or acetyl CoA carboxylase, or with mitochondrial membranes. Inhibition of ATP citrate lyase activity by L-glutamate was investigated. The activity in crude supernatants of brain, and liver from normal fed rats, was inhibited by 60%; that from liver of starved and refed rats was inhibited by 36%. Experimental evidence suggests that this inhibition is not due to a simple allosteric effect of glutamate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry