In enzymology, a S-(hydroxymethyl)glutathione dehydrogenase (EC 1.1.1.284) is an enzyme that catalyzes the chemical reaction

S-(hydroxymethyl)glutathione + NAD(P)+ ${\displaystyle \rightleftharpoons }$ S-formylglutathione + NAD(P)H + H⁺

The 3 substrates of this enzyme are S-(hydroxymethyl)glutathione, NAD⁺, and NADP⁺, whereas its 4 products are S-formylglutathione, NADH, NADPH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is S-(hydroxymethyl)glutathione:NAD⁺ oxidoreductase. Other names in common use include NAD-linked formaldehyde dehydrogenase (incorrect), formaldehyde dehydrogenase (incorrect), formic dehydrogenase (incorrect), class III alcohol dehydrogenase, ADH3, &chi, -ADH, FDH (incorrect), formaldehyde dehydrogenase (glutathione) (incorrect), GS-FDH (incorrect), glutathione-dependent formaldehyde dehydrogenase (incorrect), NAD-dependent formaldehyde dehydrogenase, GD-FALDH, and NAD- and glutathione-dependent formaldehyde dehydrogenase. This enzyme participates in methane metabolism.

As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 2FZE and 2FZW.

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