Free acetate production by rat hepatocytes during peroxisomal fatty acid and dicarboxylic acid oxidation.
The fate of the acetyl-CoA units released during peroxisomal fatty acid oxidation was studied in isolated hepatocytes from normal and peroxisome-proliferated rats. Ketogenesis and hydrogen peroxide generation were employed as indicators of mitochondrial and peroxisomal fatty acid oxidation, respectively. Butyric and hexanoic acids were employed as mitochondrial substrates, 1, omega-dicarboxylic acids as predominantly peroxisomal substrates, and lauric acid as a substrate for both mitochondria and peroxisomes. Ketogenesis from dicarboxylic acids was either absent or very low in normal and peroxisome-proliferated hepatocytes, but free acetate release was detected at rates that could account for all the acetyl-CoA produced in peroxisomes by dicarboxylic and also by monocarboxylic acids. Mitochondrial fatty acid oxidation also led to free acetate generation but at low rates relative to ketogenesis. The origin of the acetate released was confirmed employing [1-14C]dodecanedioic acid. Thus, the activity of peroxisomes might contribute significantly to the free acetate generation known to occur during fatty acid oxidation in rats and possibly also in humans.
Leighton
F
F
Departmentó de Biología Celular y Molecular, Universidad Católica de Chile, Casilla, Santiago.
Bergseth
S
S
Rørtveit
T
T
Christiansen
E N
EN
Bremer
J
J
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002478:Cells, Cultured; D003998:Dicarboxylic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D007657:Ketone Bodies; D006861:Hydrogen Peroxide; D001629:Bezafibrate