Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proton translocation coupled to quinone reduction by reduced nicotinamide--adenine dinucleotide in rat liver and ox heart mitochondria.

ABSTRACT: Measurements were made of the stoicheiometry of proton-translocation coupled to NAD(P)H oxidation by several quinones (duroquinone, ubiquinone(0), ubiquinone(1), ubiquinone(2)) in mitochondria from rat liver and ox heart. Observed stoicheiometries of protons translocated per mol of NADH oxidized (-->H(+)/2e(-) ratios; Mitchell, 1966) ranged from 0.75 (rat liver mitochondria with ubiquinone(1)) to 1.55 (ox heart mitochondria with ubiquinone(1) or ubiquinone(2)). Only the rotenone-sensitive pathway of NADH oxidation by quinone was able to support proton translocation. Correction of the observed -->H(+)/2e(-) ratios for the loss of reducing equivalents to the rotenone-insensitive pathway increased their value to approx. 2.0. It is concluded that the rotenone-sensitive NADH- ubiquinone reductase activity of the respiratory chain may be organized in the mitochondrial membrane as a proton-translocating oxidoreduction loop. The number of such loops between NADH and ubiquinone is one, and not two, as initially proposed by Mitchell (1966).

SUBMITTER: Lawford HG

PROVIDER: S-EPMC1174553 | biostudies-other | 1972 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Two Different Methods of Quantification of Oxidized Nicotinamide Adenine Dinucleotide (NAD+) and Reduced Nicotinamide Adenine Dinucleotide (NADH) Intracellular Levels: Enzymatic Coupled Cycling Assay and Ultra-performance Liquid Chromatography (UPLC)-Mass Spectrometry.

Project description:Current studies on the age-related development of metabolic dysfunction and frailty are each day in more evidence. It is known, as aging progresses, nicotinamide adenine dinucleotide (NAD+) levels decrease in an expected physiological process. Recent studies have shown that a reduction in NAD+ is a key factor for the development of age-associated metabolic decline. Increased NAD+ levels in vivo results in activation of pro-longevity and health span-related factors. Also, it improves several physiological and metabolic parameters of aging, including muscle function, exercise capacity, glucose tolerance, and cardiac function in mouse models of natural and accelerated aging. Given the importance of monitoring cellular NAD+ and NADH levels, it is crucial to have a trustful method to do so. This protocol has the purpose of describing the NAD+ and NADH extraction from tissues and cells in an efficient and widely applicable assay as well as its graphic and quantitative analysis.

| S-EPMC6086385 | biostudies-literature

Nicotinamide adenine dinucleotide as a photocatalyst.

Project description:Nicotinamide adenine dinucleotide (NAD+) is a key redox compound in all living cells responsible for energy transduction, genomic integrity, life-span extension, and neuromodulation. Here, we report a new function of NAD+ as a molecular photocatalyst in addition to the biological roles. Our spectroscopic and electrochemical analyses reveal light absorption and electronic properties of two π-conjugated systems of NAD+. Furthermore, NAD+ exhibits a robust photostability under UV-Vis-NIR irradiation. We demonstrate photocatalytic redox reactions driven by NAD+, such as O2 reduction, H2O oxidation, and the formation of metallic nanoparticles. Beyond the traditional role of NAD+ as a cofactor in redox biocatalysis, NAD+ executes direct photoactivation of oxidoreductases through the reduction of enzyme prosthetic groups. Consequently, the synergetic integration of biocatalysis and photocatalysis using NAD+ enables solar-to-chemical conversion with the highest-ever-recorded turnover frequency and total turnover number of 1263.4 hour-1 and 1692.3, respectively, for light-driven biocatalytic trans-hydrogenation.

| S-EPMC6641943 | biostudies-literature

Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD).

Project description:Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.

| S-EPMC6739475 | biostudies-literature

The interaction of reduced nicotinamide--adenine dinucleotide phosphate with reduced nicotinamide--adenine dinucleotide--ubiquinone reductase from bovine heart mitochondria.

Project description:Reduction of the chromophores of mitochondrial NADH-ubiquinone reductase by NADPH reaches only 50% of the extent of reduction by NADH, monitored at 450 nm. This effect is due to autoxidation of an enzyme component at a higher rate than its reduction by NADPH.

| S-EPMC1163948 | biostudies-other

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration.

Project description:The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR.ConclusionNAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630).

| S-EPMC5258848 | biostudies-literature

Nicotinamide adenine dinucleotide reduced (NADH) is a natural UV filter of certain bird lens

Project description:In this work, we for the first time report the identification of UV filters in the bird eye lens. We found that lenses of some raptors (black kite, common buzzard) and waterfowl (birds from Podicipedidae family) contain unusually high levels of reduced nicotinamide adenine dinucleotide (NADH)—a compound with high absorption in the UV-A range with a maximum at 340 nm. The lens metabolome of these birds also features an extremely low [NAD +]/[NADH] ratio. Chemometric analysis demonstrates that the differences between the metabolomic compositions of lenses with low and high NADH abundances should be attributed to the taxonomic features of bird species rather to the influence of the low [NAD +]/[NADH] ratio. We attributed this observation to the low metabolic activity in lens fiber cells, which make up the bulk of the lens tissue. Photochemical measurements show that properties of NADH as a UV filter are as good as that of UV filters in the human lens, including strong absorption in the UV-A spectral region, high photostability under both aerobic and anaerobic conditions, low yields of triplet state, fluorescence, and radicals under irradiation. Lenticular UV filters protect the retina and the lens from photo-induced damages and improve the visual acuity by reducing chromatic aberrations; therefore, the results obtained contribute to our understanding of the extremely high acuity of the raptor vision.

| S-EPMC9546832 | biostudies-literature

Nicotinamide adenine dinucleotide is transported into mammalian mitochondria.

Project description:Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.

| S-EPMC6013257 | biostudies-literature

Biogenesis and Homeostasis of Nicotinamide Adenine Dinucleotide Cofactor.

Project description:Universal and ubiquitous redox cofactors, nicotinamide adenine dinucleotide (NAD) and its phosphorylated analog (NADP), collectively contribute to approximately 12% of all biochemical reactions included in the metabolic model of Escherichia coli K-12. A homeostasis of the NAD pool faithfully maintained by the cells results from a dynamic balance in a network of NAD biosynthesis, utilization, decomposition, and recycling pathways that is subject to tight regulation at various levels. A brief overview of NAD utilization processes is provided in this review, including some examples of nonredox utilization. The review focuses mostly on those aspects of NAD biogenesis and utilization in E. coli and Salmonella that emerged within the past 12 years. The first pyridine nucleotide cycle (PNC) originally identified in mammalian systems and termed the Preiss-Handler pathway includes a single-step conversion of niacin (Na) to NaMN by nicotinic acid phosphoribosyltransferase (PncB). In E. coli and many other prokaryotes, this enzyme, together with nicotinamide deamidase (PncA), compose the major pathway for utilization of the pyridine ring in the form of amidated (Nm) or deamidated (Na) precursors. The existence of various regulatory mechanisms and checkpoints that control the NAD biosynthetic machinery reflects the importance of maintaining NAD homeostasis in a variety of growth conditions. Among the most important regulatory mechanisms at the level of individual enzymes are a classic feedback inhibition of NadB, the first enzyme of NAD de novo biosynthesis, by NAD and a metabolic regulation of NadK by reduced cofactors.

| S-EPMC4229845 | biostudies-literature

pH-Dependent Flavin Adenine Dinucleotide and Nicotinamide Adenine Dinucleotide Ultraviolet Resonance Raman (UVRR) Spectra at Intracellular Concentration.

Project description:The ultraviolet resonance Raman spectra of the adenine-containing enzymatic redox cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide in aqueous solution of physiological concentration are compared with the aim of distinguishing between them and their building block adenine in potential co-occurrence in biological materials. At an excitation wavelength of 266 nm, the spectra are dominated by the strong resonant contribution from adenine; nevertheless, bands assigned to vibrational modes of the nicotinamide and the flavin unit are found to appear at similar signal strength. Comparison of spectra measured at pH 7 with data obtained pH 10 and pH 3 shows characteristic changes when pH is increased or lowered, mainly due to deprotonation of the flavin and nicotinamide moieties, and protonation of the adenine, respectively.

| S-EPMC8320563 | biostudies-literature

Mechanism of proton-coupled quinone reduction in Photosystem II.

Project description:Photosystem II uses light to drive water oxidation and plastoquinone (PQ) reduction. PQ reduction involves two PQ cofactors, Q(A) and Q(B), working in series. Q(A) is a one-electron carrier, whereas Q(B) undergoes sequential reduction and protonation to form Q(B)H(2). Q(B)H(2) exchanges with PQ from the pool in the membrane. Based on the atomic coordinates of the Photosystem II crystal structure, we analyzed the proton transfer (PT) energetics adopting a quantum mechanical/molecular mechanical approach. The potential-energy profile suggests that the initial PT to Q(B)(•-) occurs from the protonated, D1-His252 to Q(B)(•)(-) via D1-Ser264. The second PT is likely to occur from D1-His215 to Q(B)H(-) via an H-bond with an energy profile with a single well, resulting in the formation of Q(B)H(2) and the D1-His215 anion. The pathway for reprotonation of D1-His215(-) may involve bicarbonate, D1-Tyr246 and water in the Q(B) site. Formate ligation to Fe(2+) did not significantly affect the protonation of reduced Q(B), suggesting that formate inhibits Q(B)H(2) release rather than its formation. The presence of carbonate rather than bicarbonate seems unlikely because the calculations showed that this greatly perturbed the potential of the nonheme iron, stabilizing the Fe(3+) state in the presence of Q(B)(•-), a situation not encountered experimentally. H-bonding from D1-Tyr246 and D2-Tyr244 to the bicarbonate ligand of the nonheme iron contributes to the stability of the semiquinones. A detailed mechanistic model for Q(B) reduction is presented.

| S-EPMC3549079 | biostudies-other

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