Dehydrogenase dehydrogenates 17-HDHA to 17-oxo-DHA

Stable Identifier
Reaction [transition]
Homo sapiens
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When acetylated by aspirin, dimeric acetylated-cyclooxygenase 2 (Ac-PTGS2 dimer aka COX2) in macrophages is able to form 17-hydroxy-docosahexaenoic acid (17-HDHA). This intermediate is then dehydrogenated by an unknown dehydrogenase to form the electrophilic oxo (EFOX) product 17-oxo-docosahexaenoic acid (17-oxo-DHA) (Groeger et al. 2010). Potential candidate enzymes are cellular dehydrogenases such as 3α-hydroxysteroid dehydrogenases (3α-HSDs), which can convert 13- and 17-HDHA into corresponding EFOXs in the presence of NAD(P)+ in vitro(supplementary data, Groeger et al. 2010) or 5- and 15-hydroxyeicosanoid dehydrogenases (5- and 15-HEDH), which convert LOX products to 5-and 15-oxoETE (Erlemann et al. 2007, Wendell et al. 2015). Anti-inflammatory actions of 17-oxo-DHA include acting as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist to inhibit pro-inflammatory cytokine and nitric oxide production (Groeger et al. 2010, Cipollina et al. 2016). 17-oxo-DHA was also found to be a strong inducer of the anti-oxidant response, promoting Nrf2 nuclear accumulation, leading to the expression of heme oxygenase 1 and more than doubling glutathione levels (Cipollina et al. 2014).
Literature References
PubMed ID Title Journal Year
20436486 Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids

Cipollina, C, Schopfer, FJ, Cole, MP, Rudolph, V, Freeman, BA, Groeger, AL, Rudolph, TK, Bonacci, G, Woodcock, SR

Nat. Chem. Biol. 2010
Catalyst Activity

aldo-keto reductase (NADP) activity of Dehydrogenase [cytosol]

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