Ketogenesis from oleate and octanoate in isolated rat hepatocytes.
Isolated hepatocytes were prepared from 48-hour starved male rats and incubated for 45 minutes with either 2.0 mM oleate or 2.0 mM octanoate. In an attempt to clarify the mechanism of antiketogenesis seen with 10.0 mM lactate, pyruvate, fructose, glycerol, ethanol and acetaldehyde, the metabolic inhibitors of alpha-2-amino-4-methoxy-trans-3-butenoic acid, n-butyl malonate and 3-mercaptopicolinic acid were added separately to the incubations. Experimental design eliminated increased esterification of fatty acids with alpha-glycerolphosphate or carnitine transferase as potential mechanisms of antiketogenis. Thus, availability of mitochondrial oxaloacetate and competitive oxidation were two potential mechanisms studied in these experiments. The data indicate that under the experimental conditions of this study the control of ketogenesis is related to both the availability of mitochondrial oxaloacetate and competitive oxidation with the relative importance depending upon the specific antiketogenic agent present. Results obtained with combinations of antiketogenic agents plus metabolic inhibitors showed that: a) fructose and glycerol antiketogenicity depends largely on increasing mitochondrial oxaloacetate; b) lactate and pyruvate depend upon both mechanisms, and c) acetaldehyde and ethanol depend primarily on competitive oxidation.
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D007657:Ketone Bodies / Q000096:biosynthesis*; D007773:Lactates / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008314:Malonates / Q000494:pharmacology; D009829:Oleic Acids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010848:Picolinic Acids / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats
D000613:Aminobutyrates; D002210:Caprylates; D007657:Ketone Bodies; D007773:Lactates; D008314:Malonates; D009829:Oleic Acids; D010848:Picolinic Acids; D011773:Pyruvates; C000264:2-amino-4-methoxy-3-butenoic acid; C027734:n-butylmalonic acid; C008363:3-mercaptopicolinic acid