Medium- and short-chain dehydrogenase/reductase gene and protein families

Abstract

Alcohol dehydrogenase 3 (ADH3) is highly conserved, ubiquitously expressed in mammals and involved in essential cellular pathways. A large active site pocket entails special substrate specificities: shortchain alcohols are poor substrates, while medium-chain alcohols and particularly the glutathione adducts S-hydroxymethylglutathione (HMGSH) and S-nitrosoglutathione (GSNO) are efficiently converted under concomitant use of NAD(+)/NADH. By oxidation of HMGSH, the spontaneous glutathione adduct of formaldehyde, ADH3 is implicated in the detoxification of formaldehyde. Through the GSNO reductase activity, ADH3 can affect the transnitrosation equilibrium between GSNO and S-nitrosated proteins, arguing for an important role in NO homeostasis. Recent findings suggest that ADH3-mediated GSNO reduction and subsequent product formation responds to redox states in terms of NADH availability and glutathione levels. Finally, a dual function of ADH3 is discussed in view of its potential implications for asthma.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

“…ADH5 (also termed ALD3) is the key FA-metabolizing enzyme (Staab et al 2008). Expression of mRNA of ADH5 in peripheral leucocytes was not affected by FA exposures in a controlled chamber study with 4 h of FA exposure per day for 5 days with FA concentrations between 0.3 and 0.7 ppm and with peaks up to 0.8 ppm (Zeller et al 2011).…”

Respiratory Substrates Regulate S-Nitrosylation of Mitochondrial Proteins through a Thiol-Dependent Pathway

“…59 The former, also known as alcohol dehydrogenase-3, is ubiquitously distributed and strongly influenced by the cellular redox potential as determined by GSH and NADH levels. 60 GSNOR activity is influenced by GSH redox status but does not require GSH for activity. The fact that DTT treatment could not reverse S-nitrosylation when thiols (GSH and/or thioredoxin) were depleted by CDNB suggests that a certain level of thioredoxin and/or GSH is essential for denitrosylation of proteins in mitochondria.…”

S-Nitrosoglutathione Reductase: A Key Regulator of S-Nitrosylation in Plant Development and Stress Responses

“…However, later the NADH-dependent reduction of GSNO, leading to the formation of oxidised glutathione (GSSG) and ammonium, has been uncovered as a more physiologically relevant reaction (Liu et al 2001;Jensen et al 1998;Staab et al 2008b). For this reason, although this designation has not been yet accepted by IUBMB nomenclature commission, the denomination of this enzyme as GSNOR is currently highly extended within scientific literature.…”

“…For this reason, although this designation has not been yet accepted by IUBMB nomenclature commission, the denomination of this enzyme as GSNOR is currently highly extended within scientific literature. According to formal enzyme classification, GSNOR belongs to a family of Zn-dependent class III alcohol dehydrogenases (ADH3; EC 1.1.1.1), which is distinct from members of class I ADH family by their high affinity towards long-chain alcohols (Koivusalo and Uotila 1991;Staab et al 2008b).…”

“…Formaldehyde can be formed also in other oxidative and demethylation reactions, like decarboxylation of glyoxylate and cytochrome P450-dependent oxidation of pesticides (Espunya et al 2006). ADH3 can be considered the most effective formaldehyde-metabolising enzyme in vitro (Staab et al 2008b). NAD + -dependent oxidation of S-(hydroxymethyl)glutathione (HMGSH), spontaneous adduct of formaldehyde with major intracellular thiol glutathione, catalysed by ADH3 thus represents a key step in the detoxification of exo-and endogenous formaldehyde.…”