Biomaterial Database

Oxidation of polyethylene glycols by alcohol dehydrogenase. 1989

D A Herold, and K Keil, and D E Bruns

Department of Pathology, University of Virginia, Charlottesville 22908.

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.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000429	Alcohol Oxidoreductases	A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).	Carbonyl Reductase,Ketone Reductase,Carbonyl Reductases,Ketone Reductases,Oxidoreductases, Alcohol,Reductase, Carbonyl,Reductase, Ketone,Reductases, Carbonyl,Reductases, Ketone
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia