| Description | Formaldehyde, a toxic metabolite because it reacts easily with protein or DNA, naturally combines with reduced glutathione (GSH) to form S-hydroxymethyl-glutathione. In some species, this reaction is accelerated by the enzyme S-(hydroxymethyl)glutathione synthase, also called glutathione-dependent formaldehyde activating enzyme. A class III alcohol dehydrogenase, with activity for a variety of medium chain alcohols (but poor activity for ethanol) can convert S-(hydroxymethyl)glutathione to S-formylglutathione, and therefore has been called glutathione-dependent formaldehyde dehydrogenase but is more properly called S-(hydroxymethyl)glutathione dehydrogenase for this activity. Finally, S-formylglutathione is converted to glutathione and formate by S-formylglutathione hydrolase, which has a dual role as a broadly specific esterase, called esterase D in animals. While the two essential enzymes of this pathway both have broad specificities, the pairing in operons in so many genomes demonstrates the recurring importance of formaldehyde detoxification. |
