NAD(P)H-hydrate epimerase

Definition:

Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. Accelerates cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis.

References:

[1]. Jun Peng, et al. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010 Jun;40(6):1738-47. [Content Brief]

[2]. Longhou Fang, et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature. 2013 Jun 6;498(7452):118-22. [Content Brief]

[3]. David Siegel, et al. NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol. 2004 May;65(5):1238-47. [Content Brief]

[4]. Kow Essuman, et al. TIR Domain Proteins Are an Ancient Family of NAD+-Consuming Enzymes. Curr Biol. 2018 Feb 5;28(3):421-430.e4. [Content Brief]

[5]. Heather S Loring, et al. Identification of the first noncompetitive SARM1 inhibitors. Bioorg Med Chem. 2020 Sep 15;28(18):115644. [Content Brief]

[6]. Yuefeng Jiang, et al. The NAD+-mediated self-inhibition mechanism of pro-neurodegenerative SARM1. Nature. 2020 Dec;588(7839):658-663. [Content Brief]

[7]. Josiah Gerdts, et al. SARM1 activation triggers axon degeneration locally via NAD⁺ destruction. Science. 2015 Apr 24;348(6233):453-7. [Content Brief]

[8]. Li Wan, et al. TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death. Science. 2019 Aug 23;365(6455):799-803. [Content Brief]

[9]. Shane Horsefield, et al. NAD+ cleavage activity by animal and plant TIR domains in cell death pathways. Science. 2019 Aug 23;365(6455):793-799. [Content Brief]

[10]. S Chen, et al. Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse. J Biol Chem. 1997 Jan 17;272(3):1437-9. [Content Brief]

[11]. Gad Asher, et al. A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev. 2005 Feb 1;19(3):316-21. [Content Brief]

[12]. Michael Carty, et al. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006 Oct;7(10):1074-81. [Content Brief]

[13]. Zhi Ying Zhao, et al. A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death. iScience. 2019 May 31;15:452-466. [Content Brief]

[14]. Eirini Meimaridou, et al. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet. 2012 May 27;44(7):740-2. [Content Brief]

[15]. Heather S Loring, et al. Initial Kinetic Characterization of Sterile Alpha and Toll/Interleukin Receptor Motif-Containing Protein 1. Biochemistry. 2020 Mar 3;59(8):933-942. [Content Brief]

[16]. Daniel W Summers, et al. SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6271-E6280. [Content Brief]

[17]. Laura S Kremer, et al. NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood. Am J Hum Genet. 2016 Oct 6;99(4):894-902. [Content Brief]

[18]. Kow Essuman, et al. The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration. Neuron. 2017 Mar 22;93(6):1334-1343.e5. [Content Brief]

[19]. Encarnación Medina-Carmona, et al. Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism. Sci Rep. 2017 Mar 14;7:44532. [Content Brief]

[20]. Nicole T Liberati, et al. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6593-8. [Content Brief]

[21]. Hitoshi Murata, et al. c-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration. J Biol Chem. 2018 Dec 7;293(49):18933-18943. [Content Brief]

[22]. D Siegel, et al. The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant. Mol Pharmacol. 1997 Aug;52(2):300-5. [Content Brief]

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