Dicarboxylic acids are prominent features of several diseases, including
Reye's syndrome. Long-chain
dicarboxylic acids have profound effects on the function and structure of isolated mitochondria, suggesting that they could contribute to the
mitochondrial dysfunction in
Reye's syndrome. Binding of
fatty acids to
albumin and the intracellular
fatty acid-binding proteins is important in regulating the transport and metabolism of
fatty acids and protects against the toxic effects of unbound
fatty acids. We studied the binding of
dicarboxylic acids to defatted
albumin using equilibrium dialysis to assess to what extent
dicarboxylic acids are likely to be bound in the plasma of patients.
Dicarboxylic acids bind weakly to
albumin in a molar ratio of 3.8, 4.2, 1.6, 0.8, and 0.7 to 1 for octadecanedioic, hexadecanedioic, tetradecanedioic, dodecanedioic, and
decanedioic acid, respectively. The dissociation constants for long-chain
dicarboxylic acids are 100-1,000-fold larger than those of comparable monocarboxylic
acids.
Oleate competes with dicarboxylic
acid and reduces the moles of dicarboxylic
acid bound per mol of
albumin to less than 1.
Octanoate inhibits dicarboxylic
acid binding. Our observations indicate that in
Reye's syndrome, substantial concentrations of
dicarboxylic acids of patients may be free and potentially toxic to mitochondria and other cellular processes.