The Janus face of alcohol dehydrogenase 3

Claudia A. Staab, Johan Ålander, Ralf Morgenstern, Roland Grafström, Jan-Olov Höög (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

41 Citations (Scopus)


Many carbonyl metabolizing enzymes are equally involved in xenobiotic and endogenous metabolism, but few have been investigated in terms of substrate competition and interference between different cellular pathways. Mammalian alcohol dehydrogenase 3 (ADH3) represents the key enzyme in the formaldehyde detoxification pathway by oxidation of S-hydroxymethylglutathione [HMGSH; the glutathione (GSH) adduct of formaldehyde]. In addition, several studies have established ADH3 as S-nitrosoglutathione (GSNO) reductase in endogenous NO homeostasis during the last decade. GSNO depletion associates with various diseases including asthma, and evidence for a causal relationship between ADH3 and asthma pathology has been put forward. In a recent study, we showed that ADH3-mediated alcohol oxidation, including HMGSH oxidation, is accelerated in presence of GSNO which is concurrently reduced under immediate cofactor recycling [C.A. Staab, J. Ålander, M. Brandt, J. Lengqvist, R. Morgenstern, R.C. Grafström, J.-O. Höög, Reduction of S-nitrosoglutathione by alcohol dehydrogenase 3 is facilitated by substrate alcohols via direct cofactor recycling and leads to GSH-controlled formation of glutathione transferase inhibitors, Biochem. J. 413 (2008) 493–504]. Thus, considering the usually low cytosolic free NADH/NAD+ ratio, formaldehyde may trigger and promote GSNO reduction by enzyme-bound cofactor recycling. These findings provided evidence for formaldehyde-induced, ADH3-mediated GSNO depletion with potential direct implications for asthma. Furthermore, analysis of product formation as a function of GSH concentrations suggested that, under conditions of oxidative stress, GSNO reduction can lead to the formation of glutathione sulfinamide and its hydrolysis product glutathione sulfinic acid, both potent inhibitors of glutathione transferase activity.
Original languageEnglish
Pages (from-to)29-35
JournalChemico-Biological Interactions
Issue number1-3
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed
Event14th International Workshop on the Enzymology and Molecular Biology of Carbonyl Metabolism - Kranjska Gora, Slovenia
Duration: 8 Jul 200812 Jul 2008


  • Asthma
  • Alcohol dehydrogenase
  • Formaldehyde dehydrogenase
  • Glutathione
  • Metabolic interaction
  • S-nitrosoglutathione


Dive into the research topics of 'The Janus face of alcohol dehydrogenase 3'. Together they form a unique fingerprint.

Cite this