From Australia to Chinchilla to Jamaica

Abstract

A general impairment of liver mitochondrial enzymes is central to Reye's syndrome (RS). The respiration of isolated liver mitochondria was measured after the addition of concentrated normal serum or RS serum derived from 12 patients. RS serum stimulates oxygen consumption in isolated rat liver mitochondria. This effect is due to (a) the oxidation of uric acid by peroxisomes contaminating the preparation and (b) a stimulation of mitochondrial respiration (1.05 ± 0.14 nmole of O2/ min · mg of protein; control 0.30 ± 0.08 nmole O2/min · mg). The stimulation of respiration occurs in the presence of all respiratory substrates, is dependent on the amount of serum added, and represents an uncoupling of oxidativephosphorylation. RS serum reduces ATP formation by 15 to 76%. The uncoupling effect correlates with the amount of free fatty acid in the serum sample and resembles theeffect induced by the addition of a dicarboxylic fatty acid. Dicarboxylic fatty acids, especially long-chain dicarboxylic acids, impair ATP formation. Dicarboxylic acids were found in the serum of all RS patients and comprised as much as 54% of the total serum free fatty acids. Ninety percent of the serum dicarboxylic acids were of 16 to 18 carbon lengths. The amount of dicarboxylic acids in the RS serum corresponded directly with the reduction in ATP formation by the RS serum. This demonstrates that dicarboxylic acids occur in RS and may be important in the general impairment of mitochondrial function in RS and other disorders where they are present.