NAD(P)H-hydrate epimerase (NAXE)

NAD(P)H-hydrate epimerase (NAXE) is an enzyme responsible for repairing unwanted hydration damage to the cofactors NADH and NADPH, which are central to cellular energy and redox metabolism[1][3]. The enzyme catalyzes the interconversion between the R and S epimers of NAD(P)HX, allowing the S-epimer to be reconverted to functional NAD(P)H by NAD(P)HX dehydratase[1]. Deficiency of NAXE leads to cellular accumulation of cyclic NADHX and is clinically linked to a rare, lethal, progressive neurodegenerative disorder marked by encephalopathy and cerebral edema[1][3]. In addition to its established metabolite repair role, NAXE appears to "moonlight" in vitamin B6 metabolism and binds apolipoprotein A-I, suggesting potential links to HDL function, cholesterol transport, and possibly angiogenesis[1]. The enzyme is widely distributed in mammalian tissues (cytosol, mitochondria, and extracellular fluids)[2], and its dysfunction severely disrupts neural and possibly metabolic health. **Note:** There are currently no approved drugs directly targeting NAXE, and no specific therapeutic agents or widely recognized clinical biomarkers beyond those described for research and diagnostic contexts.

Other names

NADHX epimeraseNAD(P)HX epimeraseNAXEAIBPAPOA1BPYJEFN1AI-BPYjeF_N1MGC119143MGC119144MGC119145Apolipoprotein A-I-binding proteinYjeF N-terminal domain-containing protein 1apoA-I binding proteinPEBEL

Drugs would modulate formation or removal of NAD(P)HX epimers (hypothetically, via inhibiting or enhancing epimerase activity)