ADH5
ADH5 (alcohol dehydrogenase 5, class III, chi polypeptide) is a zinc-containing alcohol dehydrogenase that oxidises S-(hydroxymethyl)glutathione and long-chain primary alcohols. It is also known as ADH-3, ADHX, GSNOR and formaldehyde dehydrogenase (FDH), and it acts as an S-nitrosoglutathione reductase. Browse Assay Genie's current range of ADH5 research reagents below, or read on for the biology behind the target.
ADH5 catalyses the oxidation of long-chain primary alcohols and of S-(hydroxymethyl)glutathione, the spontaneous adduct of formaldehyde and glutathione. Through this activity it is required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. The enzyme also oxidises long-chain omega-hydroxy fatty acids such as 20-HETE, producing the intermediate aldehyde 20-oxoarachidonate and the end product (5Z,8Z,11Z,14Z)-eicosatetraenedioate, a dicarboxylic acid.
A second activity gives the protein its alternative name, GSNOR. ADH5 acts as an S-nitrosoglutathione reductase, catalysing the NADH-dependent reduction of S-nitrosoglutathione and thereby regulating protein S-nitrosylation. Unlike other members of the family, class III ADH is remarkably ineffective at oxidising ethanol, so its physiological role lies in formaldehyde and nitrosative metabolism rather than ethanol handling. Formaldehyde is a potent irritant and sensitizing agent, and ADH5 is an important component of its elimination.
The ADH5 gene encodes a member of the zinc-containing alcohol dehydrogenase family, class-III subfamily, and the encoded protein forms a homodimer. It belongs to the HGNC gene group of alcohol dehydrogenases, whose members metabolise substrates including ethanol, retinol, other aliphatic alcohols, hydroxysteroids and lipid peroxidation products. The human genome also contains several non-transcribed pseudogenes related to this gene. The protein is cytoplasmic, and mouse and rat orthologs are designated Adh5. The historical name formaldehyde dehydrogenase reflects the substrate through which the enzyme was first characterised.
ADH5 is required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
As an S-nitrosoglutathione reductase, ADH5 regulates protein S-nitrosylation through NADH-dependent reduction of S-nitrosoglutathione.
ADH5 oxidises long-chain omega-hydroxy fatty acids such as 20-HETE to an aldehyde intermediate and a dicarboxylic acid end product.
ADH5 is a class III member that oxidises long-chain primary alcohols but is remarkably ineffective with ethanol, making it a useful contrast within the family.
ADH5 oxidises S-(hydroxymethyl)glutathione and long-chain primary alcohols, which is required for clearing cellular formaldehyde. It also reduces S-nitrosoglutathione in an NADH-dependent reaction, regulating protein S-nitrosylation, and oxidises omega-hydroxy fatty acids such as 20-HETE.
Formaldehyde dehydrogenase (FDH) is the previous name, reflecting activity towards S-hydroxymethyl-glutathione, the formaldehyde-glutathione adduct. GSNOR refers to its S-nitrosoglutathione reductase activity. Other aliases are ADH-3 and ADHX; the UniProt name is alcohol dehydrogenase class-3.
Mouse and rat both have an Adh5 ortholog. Human ADH5 has virtually no activity for ethanol oxidation, unlike other alcohol dehydrogenases, but is highly active on long-chain primary alcohols and S-hydroxymethyl-glutathione. Check the datasheet of any product for its validated reactivity.
Other alcohol dehydrogenase family members involved in alcohol, retinol and aldehyde metabolism, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P11766; product specifications from Assay Genie datasheets.