Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sharma2022 - Temperature-dependent NAD biosynthesis model

ABSTRACT: A computational mathematical model of NAD biosynthesis via PncA and Nampt pathway in thermophiles. It includes the temperature dependence of the reaction rates.

SUBMITTER: Suraj Sharma

PROVIDER: MODEL2103290001 | BioModels | 2022-07-19

REPOSITORIES: BioModels

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	MODEL2103290001?filename=Sharma2022_NAD_biosynthesis.xml	Xml

Items per page:

1 - 1 of 1

Publications

Structural and kinetic isotope effect studies of nicotinamidase (Pnc1) from Saccharomyces cerevisiae.

Smith Brian C BC Anderson Mark A MA Hoadley Kelly A KA Keck James L JL Cleland W Wallace WW Denu John M JM

Biochemistry 20111229 1

Nicotinamidases catalyze the hydrolysis of nicotinamide to nicotinic acid and ammonia. Nicotinamidases are absent in mammals but function in NAD(+) salvage in many bacteria, yeast, plants, protozoa, and metazoans. We have performed structural and kinetic investigations of the nicotinamidase from Saccharomyces cerevisiae (Pnc1). Steady-state product inhibitor analysis revealed an irreversible reaction in which ammonia is the first product released, followed by nicotinic acid. A series of nicotina ...[more]

PMID: 22229411

Publication: 1/9

Similar Datasets

NAMPT-dependent NAD+ biosynthesis controls circadian metabolism in a tissue-specific manner

Project description:Molecular clocks in the periphery coordinate tissue-specific daily biorhythms by integrating input from the hypothalamic master clock and intracellular metabolic signals. One such key metabolic signal is the cellular concentration of NAD+, which oscillates along with its biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT). NAD+ levels feed back into the clock to influence rhythmicity of biological functions, yet whether this metabolic fine-tuning occurs ubiquitously across cell types and is a core clock feature is unknown. Here we show that NAMPT-dependent control over the molecular clock varies substantially between tissues. Brown adipose tissue (BAT) requires NAMPT to sustain the amplitude of the core clock, whereas rhythmicity in white adipose tissue (WAT) is only moderately dependent on NAD+ biosynthesis and the skeletal muscle clock is completely refractory to loss of NAMPT. In BAT and WAT, NAMPT differentially orchestrates oscillation of clock-controlled gene networks and the diurnality of metabolite levels. NAMPT coordinates the rhythmicity of TCA cycle intermediates in BAT, but not WAT, and loss of NAD+ abolishes these oscillations similarly to high fat diet (HFD)-induced circadian disruption. Adipose NAMPT depletion also improved the ability of animals to defend body temperature during cold stress but this is independent of time-of-day. Thus, our findings reveal that peripheral molecular clocks and metabolic biorhythms are shaped in a highly tissue-specific manner by NAMPT-dependent NAD+ synthesis.

2023-04-11 | GSE221550 | GEO

Nicotinamide Starvation of Mycobacteria Defective for de novo NAD Biosynthesis

Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37Â°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested. Three biological replicates of each of two species with one dye-flip each

2010-05-14 | E-GEOD-18909 | biostudies-arrayexpress

knock out mutant n575260-NAD biosynthesis in Arabidopsis : role of quinolinate phosphoribosyltransferase

Project description:rs11-01_nad - knock out mutant n575260 - Study of the impact of a deregulation in the NAD concentration in arabidopsis - Study of the biosynthesis of NAD in Arabidopsis. Involvment of QPRTgene using the knock out mutant N575260 from Salk. 2 dye-swap - gene knock out

2012-02-03 | E-GEOD-30976 | biostudies-arrayexpress

down/up regulation of nad biosynthesis in arabidopsis and role of l-aspartate oxidase-Down/up regulation of NAD biosynthesis in Arabidopsis : role of L-Aspartate oxidase

Project description:rs13_01_lao - down/up regulation of nad biosynthesis in arabidopsis and role of l-aspartate oxidase - Study of the biosynthesis of NAD in Arabidopsis. Involvment of L-Aspartate oxidase gene using T-DNA mutant (SAIL1145_B10) and overexpressor lines (promotor 35S, vector PCW162) at the same developmental stage (12 leaves) - Study of the biosynthesis of NAD in Arabidopsis. Involvment of L-Aspartate oxidase gene using T-DNA mutant (SAIL1145_B10) and overexpressor lines (promotor 35S, vector PCW162) at the same developmental stage (12 leaves)

2018-10-01 | GSE120564 | GEO

Down regulation of qptgene in arabidopsis-Regulation of NAD biosynthesis in Arabidopsis : role of quinolinate phosphoribosyltransferase.

Project description:rs11-08_nad2 - down regulation of qptgene in arabidopsis - Study of the biosynthesis of NAD in Arabidopsis. Involvment of QPTgene using the knock out Salk mutant N575260. - Study of the biosynthesis of NAD in Arabidopsis. Involvment of QPTgene using the knock out Salk mutant N575260. 2 dye-swap - normal vs transgenic comparison

2013-08-01 | E-GEOD-49034 | biostudies-arrayexpress

NAD Salvage Supports Serine Biosynthesis

Project description:Maintenance of NAD+ levels by mitochondrial complex I, the NAD+ salvage pathway, and other routes is an important factor in of neurodegenerative disease and cancer. Both the production of NAD+ and the metabolic enzymes that require it as a redox cofactor or substrate differ widely in abundance across cell types and conditions. Disruption in the NAD+ supply thus exerts different effects depending on the cellular NAD+ requirements existing in the cell. Pharmacological depletion of NAD+ is actively being pursued in cancer and other diseases but these effects are not fully understood. Here, we combine quantitative proteomics and metabolomics to understand the consequences of disrupting cellular NAD+ levels and find that inhibiting the NAD+ salvage pathway depletes serine biosynthesis from glucose by impeding the NAD+-dependent protein 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, breast cancers that depend on PHGDH are exquisitely sensitive to blocking the NAD+ salvage pathway. PHGDH, and the rate-limiting enzyme of NAD+ salvage are also correlated in public tumor proteome and transcript datasets. These findings are immediately translatable to the pharmacological inhibition of NAMPT in PHGDH-dependent cancers.

2018-08-14 | PXD007790 | Pride

knock out mutant n575260-NAD biosynthesis in Arabidopsis : role of quinolinate phosphoribosyltransferase

2012-02-03 | GSE30976 | GEO

Nicotinamide Starvation of Mycobacteria Defective for de novo NAD Biosynthesis

Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested.

2010-02-24 | GSE18909 | GEO

Down regulation of qptgene in arabidopsis-Regulation of NAD biosynthesis in Arabidopsis : role of quinolinate phosphoribosyltransferase.

2013-08-01 | GSE49034 | GEO

Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway

Project description:Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in diverse cellular processes including metabolism, DNA repair, and aging. NAD metabolism is critical to maintain cellular homeostasis in response to environmental signals, however, how it is impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer mammalian cells with the resistance to inhibitors of NAMPT, the rate limiting enzyme in the main vertebrate NAD salvage pathway. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a key precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. This bacteria-enabled bypass of the pharmacologically induced metabolic block in mammalian cells represents a novel paradigm in drug resistance. This host-microbe metabolic interaction also dramatically enhances the hepatic NAD-boosting efficiency of nicotinamide and nicotinamide riboside supplementation, demonstrating a crucial role of microbes, gut microbiota in particular, in systemic NAD metabolism.

2020-03-03 | GSE127750 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data