Effects of 2[5(4-chlorphenyl)pentyl]oxirane-2-carboxylate on fatty acid synthesis and fatty acid oxidation in isolated rat hepatocytes.
The effects of the hypoketonaemic and hypoglycaemic compound 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) on fatty acid synthesis and fatty acid oxidation in rat hepatocytes were examined. Two microM-POCA caused a small stimulation of fatty acid synthesis which might be due to an increased flux through pyruvate dehydrogenase. Ten to one hundred microM-POCA inhibited (40-70%) fatty acid synthesis. At low concentrations (less than or equal to 5 microM) POCA was a more powerful inhibitor of fatty acid oxidation than of synthesis, but at higher concentrations (10-100 microM) the inhibition of synthesis and oxidation was similar. One hundred microM POCA-CoA inhibited acetyl-CoA carboxylase by about 22% and 100 microM-palmitoyl-CoA by about 33%. Since POCA was a more potent inhibitor of fatty acid synthesis than palmitate, but POCA-CoA did not inhibit acetyl-CoA carboxylase more strongly than palmitoyl-CoA, it is suggested that POCA-CoA may inhibit fatty acid synthase directly.
Agius
L
L
Pillay
D
D
Alberti
K G
KG
Sherratt
H S
HS
D000103:Acetyl-CoA Carboxylase / Q000032:analysis; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis; D051381:Rats
D000214:Acyl Coenzyme A; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007657:Ketone Bodies; D011768:Pyruvate Dehydrogenase Complex; C035111:B 807-27; C040542:S-(2-(5-(4-chlorophenyl)pentyl)oxiranecarboxylate)-coenzyme A; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate; D000103:Acetyl-CoA Carboxylase