Beta-oxidation in hepatocyte cultures from mice with peroxisomal gene knockouts.
Beta-oxidation of carboxylates takes place both in mitochondria and peroxisomes and in each pathway parallel enzymes exist for each conversion step. In order to better define the substrate specificities of these enzymes and in particular the elusive role of peroxisomal MFP-1, hepatocyte cultures from mice with peroxisomal gene knockouts were used to assess the consequences on substrate degradation. Hepatocytes from mice with liver selective elimination of peroxisomes displayed severely impaired oxidation of 2-methylhexadecanoic acid, the bile acid intermediate trihydroxycholestanoic acid (THCA), and tetradecanedioic acid. In contrast, mitochondrial beta-oxidation rates of palmitate were doubled, despite the severely affected inner mitochondrial membrane. As expected, beta-oxidation of the branched chain compounds 2-methylhexadecanoic acid and THCA was reduced in hepatocytes from mice with inactivation of MFP-2. More surprisingly, dicarboxylic fatty acid oxidation was impaired in MFP-1 but not in MFP-2 knockout hepatocytes, indicating that MFP-1 might play more than an obsolete role in peroxisomal beta-oxidation.
Dirkx
Ruud
R
Laboratory of Cell Metabolism, Department of Pharmaceutical Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Meyhi
Els
E
Asselberghs
Stanny
S
Reddy
Janardan
J
Baes
Myriam
M
Van Veldhoven
Paul P
PP
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002478:Cells, Cultured; D002777:Cholestanols / Q000378:metabolism; D003652:Decanoic Acids / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D002777:Cholestanols; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D009097:Multienzyme Complexes; D010168:Palmitates; D010169:Palmitic Acids; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D002245:Carbon Dioxide; C034839:2-methylhexadecanoic acid; C022069:3,7,12-trihydroxycholestan-26-oic acid; C441251:1,14-tetradecanedioic acid