NMNAT Expression and its Relation to NAD Metabolism

Author(s): H. N. Jayaram, P. Kusumanchi, J. A. Yalowitz.

Journal Name: Current Medicinal Chemistry

Volume 18 , Issue 13 , 2011

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Abstract:

Nicotinamide mononucleotide adenylyltransferease (NMNAT), a rate-limiting enzyme present in all organisms, reversibly catalyzes the important step in the biosynthesis of NAD from ATP and NMN. NAD and NADP are used reversibly in anabolic and catabolic reactions. NAD is necessary for cell survival in oxidative stress and DNA damage. Based on their localization, three different NMNATs have been recognized, NMNAT-1 (homohexamer) in the nucleus (chromosome 1 p32-35), NMNAT-2 (homodimer) in the cytoplasm (chromosome 1q25) and NMNAT-3 (homotetramer) in the mitochondria. NMNAT also catalyzes the metabolic conversion of potent antitumor prodrugs like tiazofurin and benzamide riboside to their active forms which are analogs of NAD. NAD synthase- NMNAT acts as a chaperone to protect against neurodegeneration, injury-induced axonal degeneration and also correlates with DNA synthesis during cell cycle. Since its activity is rather low in tumor cells it can be exploited as a source for therapeutic targeting. Steps involved in NAD synthesis are being utilized as targets for chemoprevention, radiosensitization and therapy of wide range of diseases, such as cancer, multiple sclerosis, neurodegeneration and Huntingtons disease.

Keywords: Nicotinamide 5'-monucleotide adenylyltransferase, nicotinamide adenine dinucleotide, targeted therapy, tiazofurin, benzamide riboside, homohexamer, radiosensitization, neurodegeneration, Huntington's disease

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Article Details

VOLUME: 18
ISSUE: 13
Year: 2011
Page: [1962 - 1972]
Pages: 11
DOI: 10.2174/092986711795590138
Price: $58

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