NMNAT expression and its relation to NAD metabolism

H. N. Jayaram, P. Kusumanchi, J. A. Yalowitz

Research output: Contribution to journalArticle

39 Scopus citations

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 NMNAT's 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 Huntington's disease.

Original languageEnglish (US)
Pages (from-to)1962-1972
Number of pages11
JournalCurrent Medicinal Chemistry
Volume18
Issue number13
DOIs
StatePublished - May 1 2011

Keywords

  • Benzamide riboside
  • Nicotinamide 5′-monucleotide adenylyltransferase
  • Nicotinamide adenine dinucleotide
  • Targeted therapy
  • Tiazofurin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Jayaram, H. N., Kusumanchi, P., & Yalowitz, J. A. (2011). NMNAT expression and its relation to NAD metabolism. Current Medicinal Chemistry, 18(13), 1962-1972. https://doi.org/10.2174/092986711795590138