D-glucarate dehydratase (GDH)

D-glucarate dehydratase (EC 4.2.1.40) is a bacterial enzyme belonging to the enolase superfamily that catalyzes the first step in the catabolic breakdown of D-glucarate, converting it into 5-dehydro-4-deoxy-D-glucarate [1, 5, 6]. This enzyme is notably absent in humans, where D-glucaric acid is instead an end-product of the D-glucuronic acid pathway and serves as a natural inhibitor of beta-glucuronidase to support detoxification [2, 11]. The activity of D-glucarate dehydratase is primary to the metabolism of enteric bacteria like Escherichia coli and Salmonella, which can utilize D-glucarate as a sole carbon and energy source [1, 3, 5]. In clinical research, D-glucarate dehydratase is primarily relevant as a diagnostic tool used in spectroscopic assays to quantify serum D-glucarate, which acts as a biomarker for phase II liver detoxification [1, 14]. Furthermore, recent evidence suggests that the enrichment of glucarate-degrading bacteria in the gut may play a role in the pathogenesis of inflammatory bowel disease (IBD) by depleting host-protective glucarate [8]. While no clinical drugs currently target this enzyme, its distinct presence in the microbiome and structural characterization with laboratory inhibitors like xylarohydroxamate offer potential for future microbiome-modulating therapeutic strategies [5, 8].

Other names

Glucarate dehydrataseD-glucarate hydro-lyaseD-glucarate dehydrasegudDGlucDygcX

No therapeutic drugs currently target this enzyme in humans; it is primarily utilized as a reagent for enzymatic quantification of glucarate.