ABSTRACT
To determine whether the accumulation of liver triglyceride in Reye's syndrome could be due to a block in beta-oxidation of the fatty acids, the ability of Reye's and control liver homogenates from samples obtained at autopsy to oxidize fatty acids was examined. Total fatty acid oxidation as measured by oxidation of [1-14C]oleoyl CoA, which mostly represents mitochondrial activity, was comparable between the groups. Peroxisomal fatty acid oxidation was, likewise, similar despite the reported increase in the numbers and sizes of these organelles. This disparity could not be explained by an artifactual dilution of product by accumulated endogenous substrate. Inference is made that active peroxisomal beta-oxidation may contribute to the increased short chain fatty CoA content of liver which was reported earlier.
Subject(s)
Acyl Coenzyme A/metabolism , Liver/metabolism , Microbodies/metabolism , Reye Syndrome/metabolism , Autopsy , Carbon Radioisotopes , Humans , Kinetics , Oxidation-Reduction , Radioisotope Dilution Technique , Reference ValuesABSTRACT
Measurements of [1-14C]oleoyl CoA oxidation in homogenates and isolated mitochondria of skeletal muscles, hearts and livers from dystrophic C57BL/6J mice and unaffected litter-mates indicate that rates are lower in dystrophic mitochondria, but are comparable in whole homogenates. These findings are not due to differences in the endogenous concentrations of the fatty CoA esters. Qualitative and quantitative differences in the molecular weight distribution of the proteins in the mitochondria and post-mitochondrial supernatants are found in the skeletal muscles with increases in the post-mitochondrial supernatant and decreases in the mitochondria in dystrophic samples. We suggest that these results are due to increased leakiness of the mitochondrial membranes in dystrophic muscles. Such differences were not observed in preparations from normal animals.
Subject(s)
Fatty Acids/metabolism , Mitochondria, Heart/metabolism , Mitochondria, Liver/metabolism , Mitochondria, Muscle/metabolism , Muscular Dystrophy, Animal/metabolism , Proteins/metabolism , Animals , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Molecular Weight , Organ Specificity , Proteins/isolation & purification , Reference ValuesABSTRACT
Patients with Reye's syndrome who have been given aspirin are said to maintain higher-than-anticipated salicylate concentrations in blood, for longer than expected. We explored whether this could be attributed to spurious results from nonsalicylate compounds in the Trinder reaction for salicylates. All of 63 organic acids and amines examined that form colored complexes with Trinder's reagent had detectable absorbance at 540 nm at 0.2 g/L, including some endogenous compounds known to be increased in Reye's syndrome patients and many others endogenous in humans. By subjecting deproteinized sera to thin-layer chromatography and eluting the salicylate fraction before complexing it with ferric ion, true salicylate can be measured quantitatively and differentiated from interfering compounds. In addition, when we examined the effect of salicylate on palmitate binding to serum proteins, we found that salicylate concentrations of 0.2 g/L displaced [16-14C]palmitate binding to protein more in Reye's syndrome patients than in Reye's syndrome survivors or children with influenza. This suggests the presence of atypical binding characteristics for salicylate and palmitate in the acute disorder but not in survivors or children with influenza.
