| Abstrakt: |
To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4, salicylate, and carnitine on the oxidation of l-14Cpalmitic acid to acid-soluble products (ASP) and to CO2were investigated in rat liver slices, DL-carnitine (5 mM) increased total oxidation (ASP CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90 of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2(63) was larger than that of total oxidation (30). Carnitine did not influence NH4inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90 at 3 mM salicylate but that of oxidation to CO2reached 50. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4exerted a stronger inhibition of oxidation to CO2than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits. |
