Essential role ofBordetellaNadC in a quinolinate salvage pathway for NAD biosynthesis

A previously undescribed nucleoside salvage pathway for NAD biosynthesis is defined in Salmonella typhimurium. Since neither nicotinamide nor nicotinic acid is an intermediate in this pathway, this second pyridine nucleotide salvage pathway is distinct from the classical Preiss-Handler pathway. The evidence indicates that the pathway is from nicotinamide ribonucleoside to nicotinamide mononucleotide (NMN) and then to nicotinic acid mononucleotide, followed by nicotinic acid adenine dinucleotide and NAD. The utilization of exogenous NMN for NAD biosynthesis has been reexamined, and in vivo evidence is provided that the intact NMN molecule traverses the membrane.

Download Full-text

Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule

Biomolecules ◽

10.3390/biom9010034 ◽

2019 ◽

Vol 9 (1) ◽

pp. 34 ◽

Cited By ~ 15

Author(s):

Saikat Kumar Poddar ◽

Ali Ehsan Sifat ◽

Sanjana Haque ◽

Noor Ahmed Nahid ◽

Sabiha Chowdhury ◽

...

Keyword(s):

Nicotinamide Adenine Dinucleotide ◽

Biosynthetic Pathway ◽

The Other ◽

Preclinical Studies ◽

Salvage Pathway ◽

Pharmacological Activities ◽

Nicotinamide Riboside ◽

Nad Biosynthesis ◽

Nicotinamide Mononucleotide ◽

Subsequent Conversion

Nicotinamide mononucleotide (NMN) is a nucleotide that is most recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis. Although the biosynthetic pathway of NMN varies between eukaryote and prokaryote, two pathways are mainly followed in case of eukaryotic human—one is through the salvage pathway using nicotinamide while the other follows phosphorylation of nicotinamide riboside. Due to the unavailability of a suitable transporter, NMN enters inside the mammalian cell in the form of nicotinamide riboside followed by its subsequent conversion to NMN and NAD+. This particular molecule has demonstrated several beneficial pharmacological activities in preclinical studies, which suggest its potential therapeutic use. Mostly mediated by its involvement in NAD+ biosynthesis, the pharmacological activities of NMN include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity. The recent groundbreaking discovery of anti-ageing activities of this chemical moiety has added a valuable essence in the research involving this molecule. This review focuses on the biosynthesis of NMN in mammalian and prokaryotic cells and mechanism of absorption along with the reported pharmacological activities in murine model.

Download Full-text

Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis

The Plant Journal ◽

10.1111/j.1365-313x.2006.03013.x ◽

2007 ◽

Vol 49 (6) ◽

pp. 1020-1029 ◽

Cited By ~ 60

Author(s):

Guodong Wang ◽

Eran Pichersky

Keyword(s):

Salvage Pathway ◽

Nad Biosynthesis

Download Full-text

Ribosylnicotinamide Kinase Domain of NadR Protein: Identification and Implications in NAD Biosynthesis

Journal of Bacteriology ◽

10.1128/jb.184.24.6906-6917.2002 ◽

2002 ◽

Vol 184 (24) ◽

pp. 6906-6917 ◽

Cited By ~ 60

Author(s):

Oleg V. Kurnasov ◽

Boris M. Polanuyer ◽

Shubha Ananta ◽

Roman Sloutsky ◽

Annie Tam ◽

...

Keyword(s):

Drug Targets ◽

Protein Identification ◽

Kinase Domain ◽

Salvage Pathway ◽

Concerted Action ◽

Nad Metabolism ◽

Growth And Survival ◽

Nad Biosynthesis ◽

Nicotinamide Mononucleotide ◽

Serovar Typhimurium

ABSTRACT NAD is an indispensable redox cofactor in all organisms. Most of the genes required for NAD biosynthesis in various species are known. Ribosylnicotinamide kinase (RNK) was among the few unknown (missing) genes involved with NAD salvage and recycling pathways. Using a comparative genome analysis involving reconstruction of NAD metabolism from genomic data, we predicted and experimentally verified that bacterial RNK is encoded within the 3′ region of the nadR gene. Based on these results and previous data, the full-size multifunctional NadR protein (as in Escherichia coli) is composed of (i) an N-terminal DNA-binding domain involved in the transcriptional regulation of NAD biosynthesis, (ii) a central nicotinamide mononucleotide adenylyltransferase (NMNAT) domain, and (iii) a C-terminal RNK domain. The RNK and NMNAT enzymatic activities of recombinant NadR proteins from Salmonella enterica serovar Typhimurium and Haemophilus influenzae were quantitatively characterized. We propose a model for the complete salvage pathway from exogenous N-ribosylnicotinamide to NAD which involves the concerted action of the PnuC transporter and NRK, followed by the NMNAT activity of the NadR protein. Both the pnuC and nadR genes were proven to be essential for the growth and survival of H. influenzae, thus implicating them as potential narrow-spectrum drug targets.

Download Full-text

Faint Hα Emission in the Corona and Its Relation to the Prominences

International Astronomical Union Colloquium ◽

10.1017/s0252921100025550 ◽

1994 ◽

Vol 144 ◽

pp. 339-342

Author(s):

V. N. Dermendjiev ◽

Z. Mouradian ◽

J.- L. Leroy ◽

P. Duchlev

Keyword(s):

Magnetic Field ◽

Solar Corona ◽

Essential Role ◽

Hα Emission

AbstractThe relation between episodically observed in the solar corona faint Hαemission structures and the long lived prominences was studied. Particular consideration was given for cases in which the corresponding prominences had undergone DB process. An MHD interpretation of the phenomenon “emissions froides” (cool emission) is proposed in which an essential role plays the prominence supporting magnetic field.

Download Full-text

Freeze-fracture observations on changes in the distribution of Filipin-sterol complexes during epididymal maturation and capacitation of boar spermatozoa

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157991 ◽

1990 ◽

Vol 48 (3) ◽

pp. 90-91

Author(s):

N. Seki ◽

Y. Toyama ◽

T. Nagano

Keyword(s):

Plasma Membrane ◽

Essential Role ◽

Freeze Fracture ◽

Final Concentration ◽

Freeze Fracturing ◽

Physiological Conditions ◽

Epididymal Maturation ◽

Cacodylate Buffer ◽

Sperm Membrane ◽

Boar Spermatozoa

It is believed that i ntramembra.nous sterols play an essential role in membrane stability and permeability. To investigate the distribution changes of sterols in sperm membrane during epididymal maturation and capacitation, filipin has been used as a cytochemical probe for the detection for membrane sterols. Using this technique in combination with freeze fracturing, we examined the boar spermatozoa under various physiological conditions.The spermatozoa were collected from: 1) caput, corpus and cauda epididymides, 2) sperm rich fraction of ejaculates, and 3)the uterus 2hr after natural coition. They were fixed with 2.5% glutaraldehyde in 0.05M cacodylate buffer (pH 7.4), and treated with the filipin solution (final concentration : 0.02.0.05%) for 24hr at 4°C with constant agitation. After the filipin treatment, replicas were made by conventional freeze-fracture technique. The density of filipin-sterol complexes (FSCs) was determined in the E face of the plasma membrane of head regions.

Download Full-text