Oxidation of polyethylene glycols by alcohol dehydrogenase.
The present studies were undertaken to investigate the enzymology of a fatal toxic syndrome that resulted from the absorption and subsequent oxidation of polyethylene glycol (PEG). The presence of organic acids of PEG in the blood of poisoned patients and in an animal model suggested that the metabolism of PEG involved sequential oxidations by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. A key question concerned the ability of ADH to initiate this pathway for oxidation of PEG. In the present studies the oxidation of PEG homologues by ADH was characterized. The polymer homologues of ethylene glycol from n = 1 to n = 8 were used as substrates. ADH catalyzed the oxidation of each of these PEGs. The oxidation of PEG was inhibited by the ADH inhibitor 4-methylpyrazole. With the exception of diethylene glycol, the Km decreased as the homologue number increased, and the Vmax decreased progressively through the series. The concentrations of PEG in the blood of poisoned humans and animals were 0.06 to 0.8 Km of ADH for all the PEG homologues above the triethylene glycol. These investigations establish ADH as a candidate enzyme for mammalian metabolism of PEG and thus suggest that specific inhibitors of ADH may prove to be useful as tools to treat PEG poisoning.
Herold
D A
DA
Department of Pathology, University of Virginia, Charlottesville 22908.
Keil
K
K
Bruns
D E
DE
D000429:Alcohol Oxidoreductases / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000378:metabolism*
D011092:Polyethylene Glycols; D000429:Alcohol Oxidoreductases