Mechanism of the protective action of cysteine and penicillamine against acetaldehyde-induced mitochondrial injury

The inhibition of several mitochondrial functions by acetaldehyde, a metabolite of ethanol oxidation, was previously shown to be almost completely relieved by cysteine. To study the mechanism of this protective effect, several derivatives of cysteine were also tested. Free sulfhydryl and amino groups appear to be required for maximal protection against the inhibition by acetaldehyde since no protective effect was found with N-acetylcysteine or S-methylcysteine. Cysteine interacts readily with acetaldehyde whereas N-acetylcysteine and S-methylcysteine do not. Penicillamine (β,β-dimethylcysteine) also relieved the inhibition by acetaldehyde, but prior incubation of penicillamine with acetaldehyde was required. Penicillamine was not as effective as cysteine, a finding which correlates with the weaker interaction of penicillamine with acetaldehyde. The greater stability of penicillamine compared to cysteine may be an advantage in studies of the effects of sulfhydryl amino acids on acute and chronic effects of ethanol and acetaldehyde.