Metabolism of S-3-hydroxybutyrate in the perfused rat liver.
The metabolism of millimolar concentrations of S-3-hydroxybutyrate (the unnatural enantiomer) has been studied in perfused livers from fed and starved rats. Protocols were designed to test whether S-3-hydroxybutyrate is metabolized in the cytosol or in the mitochondria via a racemase, a dehydrogenase, or a ligase. Our data show that only a minor fraction of S-3-hydroxybutyrate metabolism could occur via L-3-hydroxyacid dehydrogenase. Most of the metabolism of S-3-hydroxybutyrate proceeds via mitochondrial activation. In rat liver, S-3-hydroxybutyrate is converted to physiological ketone bodies (i.e., R-3-hydroxybutyrate, acetoacetate, acetone), lipids, and CO2. Carbons from S-3-hydroxybutyrate are transferred from the mitochondria to the cytosol mostly via citrate and the citrate cleavage pathway.
Lincoln
B C
BC
Department of Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Des Rosiers
C
C
Brunengraber
H
H
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D020155:3-Hydroxybutyric Acid; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004435:Eating; D005215:Fasting; D006885:Hydroxybutyrates / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D006885:Hydroxybutyrates; D015094:3-Hydroxyacyl CoA Dehydrogenases; D020155:3-Hydroxybutyric Acid