Leukotriene B4 dehydrogenase (PTGR1) (PTGR1)

Leukotriene B4 dehydrogenase, also known as Prostaglandin reductase 1 (PTGR1), is a critical enzyme in the metabolic inactivation of eicosanoids, particularly the potent pro-inflammatory mediator leukotriene B4 (LTB4) (GeneCards, 2024; PMC3708845). By catalyzing the NADPH-dependent reduction of LTB4 into 12-keto-LTB4, the enzyme significantly reduces the biological activity of this chemoattractant, thereby playing a vital role in the resolution of inflammatory responses (PMC8343111; PMC3708845). Beyond its physiological role in lipid metabolism, PTGR1 is frequently overexpressed in various malignancies, including hepatocellular carcinoma and lung cancer, where it is associated with poor prognosis and altered tumor metabolism (PMC8343111; ResearchGate, 2024). Interestingly, PTGR1 also functions as a key activator for specific anticancer prodrugs, such as irofulven and LP-184, which require enzymatic conversion to exert their cytotoxic effects (PMC8343111; ResearchGate, 2024). This dual role makes PTGR1 a significant target for both anti-inflammatory therapies and precision oncology, where its expression levels can serve as a biomarker for drug sensitivity. Dysregulation of the PTGR1-mediated pathway is linked to chronic inflammatory diseases, metabolic disorders, and increased susceptibility to certain infections like tuberculosis (PMC3708845; PMC4579146). Consequently, modulating PTGR1 activity offers a strategic approach to managing both hyper-inflammatory states and treatment-resistant cancers.

Other names

Prostaglandin reductase 115-oxoprostaglandin 13-reductaseNADP-dependent leukotriene B4 dehydrogenaseLTB4DHZADH3Zinc-binding alcohol dehydrogenase domain-containing protein 3PGR1DIG-1

PTGR1 functions as an oxidoreductase that inactivates the pro-inflammatory mediator leukotriene B4 by converting it to 12-keto-leukotriene B4. It also acts as a metabolic activator for certain prodrugs, such as irofulven and LP-184, by reducing their alpha,beta-unsaturated ketone functional groups into active, DNA-reactive metabolites (PMC8343111; ResearchGate, 2024).