Short-term regulation of carnitine palmitoyltransferase I in cultured rat hepatocytes: spontaneous inactivation and reactivation by fatty acids.
Liver carnitine palmitoyltransferase I (CPT I), the rate-limiting enzyme of mitochondrial beta-oxidation, rapidly loses its activity when hepatocytes are put in culture. 3-Thia fatty acids reactivate the enzyme and can increase its activity 3-4-fold in 5-10 min. Normal fatty acids are also able to stimulate CPT I, but to a limited extent, compared to 3-thia fatty acid. This activation does not affect malonyl-CoA sensitivity. CPT I in hepatocytes from both fasted and fasted-carbohydrate refed rats is inactivated and reactivated to a similar extent. Free dodecylthioacetic acid (DTA) is at least as efficient as DTA-CoA as activator. CPT I activity in isolated mitochondria is not influenced by incubation with DTA, suggesting that the regulation of CPT I depends on an extramitochondrial component(s) in the cell. It is concluded that fatty acids activate pre-existing, inactive CPT I without involvement of gene transcription and independently of malonyl-CoA.
Sleboda
J
J
Institute of Medical Biochemistry, University of Oslo, Norway. jowita@basalmed.uio.no
Risan
K A
KA
Spydevold
O
O
Bremer
J
J
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008316:Malonyl Coenzyme A / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology