ACETOACETATE AND d-(-)-BETA-HYDROXYBUTYRATE AS PRECURSORS FOR STEROL SYNTHESIS BY CALF OLIGODENDROCYTES IN SUSPENSION CULTURE: EXTRAMITOCHONDRIAL PATHWAY FOR ACETOACETATE METABOLISM |
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Authors: | David Pleasure Craig Lichtman Sarah Eastman Marge Lieb Oded Abramsky Donald Silberberg |
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Institution: | Division of Experimental Child Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, U.S.A. and Department of Neurology, University of Pennsylvania, Philadelphia, PA, U.S.A. |
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Abstract: | Abstract— Oligodendroglia prepared from calf cerebral white matter were incubated with 3-14C]aceto-acetate (AcAc), d -3-14C](-)-beta-hydroxybutyrate (OHbut) or 3H2O. Addition to the medium of the ATP-rate oxaloacetate lyase inhibitor (-)-hydroxycitrate diminished sterol labelling from OHbut and 3H2O, but caused 4-fold stimulation of sterol labelling from AcAc. The discrepancy between results with the two ketone bodies indicates the existence in oligodendroglia of an extrarnitochondrial pathway for conversion of AcAc but not OHbut to acetyl CoA. Acetoacetyl CoA synthetase, the first enzyme in this pathway, was more than 20-fold enriched in oligodendroglia over whole brain. |
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