Dynamics of NAD-metabolism: everything but constant

2015 ◽  
Vol 43 (6) ◽  
pp. 1127-1132 ◽  
Author(s):  
Christiane A. Opitz ◽  
Ines Heiland
Keyword(s):  
Redox State ◽  
Complex Dynamic ◽  
Metabolic Pathway Analysis ◽  
Dynamic Changes ◽  
Nad Metabolism ◽  
Phosphorylated Form ◽  
Cyclic Adp Ribose ◽  
Messenger Molecules ◽  
Concentration Changes ◽  
Electron Carriers

NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG. In metabolic pathway analysis, the total amount of NAD is usually assumed to be constant. That means that changes in the redox state might be considered, but concentration changes of the NAD moiety are usually neglected. However, a growing number of NAD-consuming reactions have been identified, showing that this assumption does not hold true in general. NAD-consuming reactions are common characteristics of NAD+-dependent signalling pathways and include mono- and poly-ADP-ribosylation of proteins, NAD+-dependent deacetylation by sirtuins and the formation of messenger molecules such as cyclic ADP-ribose (cADPR) and nicotinic acid (NA)-ADP (NAADP). NAD-consuming reactions are thus involved in major signalling and gene regulation pathways such as DNA-repair or regulation of enzymes central in metabolism. All known NAD+-dependent signalling processes include the release of nicotinamide (Nam). Thus cellular NAD pools need to be constantly replenished, mostly by recycling Nam to NAD+. This process is, among others, regulated by the circadian clock, causing complex dynamic changes in NAD concentration. As disturbances in NAD homoeostasis are associated with a large number of diseases ranging from cancer to diabetes, it is important to better understand the dynamics of NAD metabolism to develop efficient pharmacological invention strategies to target this pathway.

scholarly journals Dynamic DNA Methylation in Plant Growth and Development

2018 ◽  
Vol 19 (7) ◽  
pp. 2144 ◽  
Author(s):  
Arthur Bartels ◽  
Qiang Han ◽  
Pooja Nair ◽  
Liam Stacey ◽  
Hannah Gaynier ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Plant Growth ◽  
Growth And Development ◽  
Genome Stability ◽  
Epigenetic Modification ◽  
Plant Growth And Development ◽  
Complex Dynamic ◽  
Dynamic Changes ◽  
The Common ◽  
Methylation Patterns

DNA methylation is an epigenetic modification required for transposable element (TE) silencing, genome stability, and genomic imprinting. Although DNA methylation has been intensively studied, the dynamic nature of methylation among different species has just begun to be understood. Here we summarize the recent progress in research on the wide variation of DNA methylation in different plants, organs, tissues, and cells; dynamic changes of methylation are also reported during plant growth and development as well as changes in response to environmental stresses. Overall DNA methylation is quite diverse among species, and it occurs in CG, CHG, and CHH (H = A, C, or T) contexts of genes and TEs in angiosperms. Moderately expressed genes are most likely methylated in gene bodies. Methylation levels decrease significantly just upstream of the transcription start site and around transcription termination sites; its levels in the promoter are inversely correlated with the expression of some genes in plants. Methylation can be altered by different environmental stimuli such as pathogens and abiotic stresses. It is likely that methylation existed in the common eukaryotic ancestor before fungi, plants and animals diverged during evolution. In summary, DNA methylation patterns in angiosperms are complex, dynamic, and an integral part of genome diversity after millions of years of evolution.

scholarly journals NAD metabolism in aging and cancer

2020 ◽  
Vol 245 (17) ◽  
pp. 1594-1614 ◽  
Author(s):  
John WR Kincaid ◽  
Nathan A Berger
Keyword(s):  
Redox Reactions ◽  
Metabolic Disorders ◽  
Therapeutic Interventions ◽  
Transport Pathways ◽  
Nad Metabolism ◽  
Regulatory Enzymes ◽  
Enzyme Substrate ◽  
Cyclic Adp Ribose ◽  
And Function ◽  
Pathologic Processes

NAD+ and its derivatives NADH, NADP+, and NADPH are essential cofactors in redox reactions and electron transport pathways. NAD serves also as substrate for an extensive series of regulatory enzymes including cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases which are O-acetyl-ADP-ribosyltransferases. As a result of the numerous and diverse enzymes that utilize NAD as well as depend on its synthesis and concentration, significant interest has developed in its role in a variety of physiologic and pathologic processes, and therapeutic initiatives have focused both on augmenting its levels as well as inhibiting some of its pathways. In this article, we examine the biosynthesis of NAD, metabolic processes in which it is involved, and its role in aging, cancer, and other age-associated comorbidities including neurodegenerative, cardiovascular, and metabolic disorders. Therapeutic interventions to augment and/or inhibit these processes are also discussed. Impact statement NAD is a central metabolite connecting energy balance and organismal growth with genomic integrity and function. It is involved in the development of malignancy and has a regulatory role in the aging process. These processes are mediated by a diverse series of enzymes whose common focus is either NAD’s biosynthesis or its utilization as a redox cofactor or enzyme substrate. These enzymes include dehydrogenases, cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases. This article describes the manifold pathways that comprise NAD metabolism and promotes an increased awareness of how perturbations in these systems may be important in disease prevention and/or progression.

scholarly journals NAD Metabolism and Cyclic ADP-Ribose.

1998 ◽  
Vol 36 (8) ◽  
pp. 497-503
Author(s):  
Kenji KONTANI ◽  
Toshiaki KATADA
Keyword(s):  
Nad Metabolism ◽  
Cyclic Adp Ribose

scholarly journals Effects of photobiomodulation on the redox state of healthy and cancer cells

2020 ◽  
Author(s):  
Clara Maria Gonçalves de Faria ◽  
Heloisa Ciol ◽  
Vanderlei Salvador Bagnato ◽  
Sebastião Pratavieira
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Redox State ◽  
Mitochondrial Metabolism ◽  
Atp Production ◽  
Distinct Cell ◽  
Irradiation Cell ◽  
Oxidase Enzyme ◽  
Oral Cancer Cells ◽  
Electron Carriers

Photobiomodulation (PBM) uses light to stimulate cells. The molecular basis of the effects of PBM is being unveiled, but it is stated that the cytochrome-c oxidase enzyme in mitochondria, a photon acceptor of PBM, contributes to an increase in ATP production and modulates the reduction and oxidation of electron carriers NADH and FAD. As it can stimulate cells, PBM is not used on tumors. Thus, it is interesting to investigate if its effects correlate to mitochondrial metabolism and if so, how it could be linked to the optical redox ratio (ORR). To that end, fibroblasts and oral cancer cells were irradiated with a light source of 780 nm and a total dose of 5 J/cm2, and imaged by optical microscopy. PBM down-regulated the SCC-25 ORR by 10%. Furthermore, PBM led to an increase in ROS and ATP production in cancer cells after 4 h, while fibroblasts only had a modest ATP increase 6 h after irradiation. Cell lines did not show distinct cell cycle profiles, as both had an increase in G2/M cells. This study indicates that PBM shifts the redox state of oral cancer cells towards glycolysis and affects normal and tumor cells through distinct pathways. To our knowledge, this is the first study that investigated the effects of PBM on mitochondrial metabolism from the initiation of the cascade to DNA replication. This is an essential step in the investigation of the mechanism of action of PBM in an effort to avoid misinterpretations of a variety of combined protocols.

scholarly journals Computational modelling of the piglet brain to simulate near-infrared spectroscopy and magnetic resonance spectroscopy data collected during oxygen deprivation

2012 ◽  
Vol 9 (72) ◽  
pp. 1499-1509 ◽  
Author(s):  
Tracy Moroz ◽  
Murad Banaji ◽  
Nicola J. Robertson ◽  
Chris E. Cooper ◽  
Ilias Tachtsidis
Keyword(s):  
Infrared Spectroscopy ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Redox State ◽  
Near Infrared ◽  
Lactate Concentration ◽  
Computational Modelling ◽  
Resonance Spectroscopy ◽  
Concentration Changes

We describe a computational model to simulate measurements from near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) in the piglet brain. Piglets are often subjected to anoxic, hypoxic and ischaemic insults, as experimental models for human neonates. The model aims to help interpret measurements and increase understanding of physiological processes occurring during such insults. It is an extension of a previous model of circulation and mitochondrial metabolism. This was developed to predict NIRS measurements in the brains of healthy adults i.e. concentration changes of oxyhaemoglobin and deoxyhaemoglobin and redox state changes of cytochrome c oxidase (CCO). We altered and enhanced the model to apply to the anaesthetized piglet brain. It now includes metabolites measured by 31 P-MRS, namely phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP). It also includes simple descriptions of glycolysis, lactate dynamics and the tricarboxylic acid (TCA) cycle. The model is described, and its simulations compared with existing measurements from piglets during anoxia. The NIRS and MRS measurements are predicted well, although this requires a reduction in blood pressure autoregulation. Predictions of the cerebral metabolic rate of oxygen consumption (CMRO 2 ) and lactate concentration, which were not measured, are given. Finally, the model is used to investigate hypotheses regarding changes in CCO redox state during anoxia.

Dynamic changes in fluid redox state associated with episodic fault rupture along a megasplay fault in a subduction zone

2011 ◽  
Vol 302 (3-4) ◽  
pp. 369-377 ◽  
Author(s):  
Asuka Yamaguchi ◽  
Stephen F. Cox ◽  
Gaku Kimura ◽  
Shin'ya Okamoto
Keyword(s):  
Subduction Zone ◽  
Redox State ◽  
Fault Rupture ◽  
Dynamic Changes

scholarly journals In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

2015 ◽  
Vol 112 (9) ◽  
pp. 2876-2881 ◽  
Author(s):  
Xiao-Hong Zhu ◽  
Ming Lu ◽  
Byeong-Yeul Lee ◽  
Kamil Ugurbil ◽  
Wei Chen
Keyword(s):  
Human Brain ◽  
Redox State ◽  
Ex Vivo ◽  
Healthy Human ◽  
Nad Metabolism ◽  
Mitochondrial Functions ◽  
Age Dependent ◽  
Nadh Redox State

NAD is an essential metabolite that exists in NAD+or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.

Sign in / Sign up

Export Citation Format

Share Document