Studies on the effects of saturated and unsaturated short-chain monocarboxylic acids on the energy metabolism of rat liver mitochondria.
The effect of eight branched-chain amino acid metabolites, four metabolites from the beta-oxidation, and the unphysiologic acid 4-pentenoic acid on the oxygen consumption rate of liver mitochondria oxidizing pyruvate, 2-oxo-glutarate, and L-palmitoylcarnitine has been investigated. The 12 metabolites are: propionic, isobutyric, 2-Me-butyric, isovaleric, acrylic, Me-acrylic, tiglic, Me-crotonic, butyric, hexanoic, crotonic, and 2-hexenoic acids. The oxidation rate of pyruvate was strongly inhibited by propionic, 4-pentenoic, and isovaleric acids at 0.1, 0.1, and 1.0 mM, respectively. With 2-oxo-glutarate as substrate, the oxygen consumption rate was strongly inhibited at 0.1 mM of propionic, 4-pentenoic, and isovaleric acids. The L-palmitoyl-carnitine oxidation rate was very strongly inhibited by 0.1 mM 4-petenoic acid, whereas butyric and hexanoic acids exerted a moderate inhibition at 0.1 mM. Propionic acid inhibited L-palmitoylcarnitine oxidation slightly at 1.0 mM. It is argued that propionyl-CoA and isovaleryl-CoA inhibit pyruvate and 2-oxo-glutarate dehydrogenases directly, and the significance of the results for ketotic episodes in organic acidurias is discussed.
D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives*; D003864:Depression, Chemical; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005977:Glutarates / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats
D000597:Amino Acids, Branched-Chain; D002264:Carboxylic Acids; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D005977:Glutarates; D011773:Pyruvates; D010172:Palmitoylcarnitine; D002331:Carnitine