This is a working overview of ADP-ribose, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-04-25 and is reviewed periodically as new material appears.
NAD+ is the oxidized form of nicotinamide adenine dinucleotide, a coenzyme built from two nucleotides joined by a phosphate linkage. One nucleotide carries adenine, and the other carries nicotinamide; the plus sign denotes a formal positive charge on the nicotinamide ring, not a free proton. In cells, NAD+ and its reduced partner NADH form a reversible redox pair. That pair participates in electron transfer reactions throughout metabolism. The abbreviation NAD+ is common in biochemistry, while NAD(H) sometimes denotes the combined pool.
The molecule was first described in the early twentieth century as a factor that promoted fermentation in yeast extracts. Later work linked it to hydrogen transfer and to the oxidation of nutrients in living tissues. Its structure was resolved as a dinucleotide, which explained why it could accept and donate electrons at specific enzyme sites. Today, NAD+ is recognized as a central substrate and signaling precursor, not merely a metabolic cofactor. Whether all observed NAD+ changes reflect causal signaling remains an open question.
In aqueous solution, NAD+ is most stable under mildly acidic to neutral conditions and degrades faster at high pH or elevated temperature. The molecule can hydrolyze at the pyrophosphate bond or undergo nonenzymatic cyclization. Buffers, chelating agents, and cold temperatures slow these losses during analysis. Repeated freeze-thaw cycles are generally avoided because they can promote degradation and concentration changes. Light exposure is also controlled, though NAD+ is less photolabile than some related nucleotides.
Commercial NAD+ is supplied as a solid, often as the free acid or a salt, and purity is verified by chromatographic methods. Laboratories typically store it desiccated at minus 20 degrees Celsius or below. Working solutions are prepared fresh because even sterile aqueous solutions can lose activity over hours to days depending on pH and temperature. Documentation may include a certificate of analysis, an assay value, and a recommended retest date. Researchers should verify identity and purity when results depend on precise cofactor concentrations.
NAD+ is commonly measured by high-performance liquid chromatography with ultraviolet detection, often at 254 or 260 nm. Enzymatic cycling assays provide higher sensitivity by coupling NAD+ to a reporter reaction. Mass spectrometry can distinguish NAD+ from close analogues and confirm isotope labeling. Sample preparation usually involves rapid quenching of metabolism to prevent interconversion with NADH. Because NAD+ and NADH differ by one hydride, extraction conditions strongly affect the measured ratio.
| Property | Value | Notes |
|---|---|---|
| Chemical name | Nicotinamide adenine dinucleotide (oxidized form) | NAD+ denotes the oxidized redox state |
| Common synonyms | Diphosphopyridine nucleotide; coenzyme I | Older names appear in historical literature |
| Molar mass | About 663.43 g/mol | Free acid value; salts and hydrates differ |
| Appearance | White to off-white powder | The purified solid is white; solutions are clear |
| Solubility | Highly soluble in water | Aqueous buffers are common laboratory solvents |
NAD+ stands for nicotinamide adenine dinucleotide, the oxidized form of a coenzyme found in all living cells. The molecule consists of two nucleotides, adenine and nicotinamide ribose, joined through phosphate groups. Its chemical formula is C21H27N7O14P2, and the free acid has a molar mass near 663.43 grams per mole. In redox reactions, NAD+ accepts a hydride ion and becomes NADH. The pair NAD+ and NADH participates in hundreds of metabolic reactions, including steps in glycolysis, the citric acid cycle, and oxidative phosphorylation.
In cells, NAD+ functions primarily as an electron carrier. Dehydrogenase enzymes in glycolysis and the citric acid cycle transfer hydride from substrates to NAD+, producing NADH. NADH then delivers electrons to the mitochondrial respiratory chain, supporting ATP synthesis. In fermentation, NADH is reoxidized to NAD+ so that glycolysis can continue. The balance between NAD+ and NADH helps set metabolic flux. Beyond redox, NAD+ serves as a substrate for enzymes that cleave it, including sirtuins, poly(ADP-ribose) polymerases, and CD38. These reactions consume NAD+ and release nicotinamide and ADP-ribose products.
Biosynthesis occurs through salvage, Preiss-Handler, and de novo pathways. In mammals, the salvage pathway from nicotinamide predominates, and NAMPT is often described as rate-limiting. Nicotinamide riboside and nicotinic acid enter related routes that converge on NAD+ production. Tissue NAD+ concentrations vary widely and are maintained by a balance of synthesis and consumption. Some studies report age-related declines in certain tissues, but whether these changes cause disease or can be reversed to improve human health remains an open question.
The nicotinamide ring undergoes reversible reduction at the para position, converting NAD+ to NADH. This reaction transfers a hydride equivalent, not a free hydrogen atom or electron alone. Because the redox pair has a defined reduction potential, it links oxidation of fuels to respiratory chain activity. Many dehydrogenases use NAD+ as a co-substrate and produce NADH. The ratio of NAD+ to NADH reflects metabolic state and influences flux through several pathways.
NAD+ also serves as a substrate for enzymes that cleave it, including sirtuins, PARPs, and CD38. These enzymes consume NAD+ and release nicotinamide and ADP-ribose or related products. The dual roles as redox cofactor and signaling substrate connect NAD+ to DNA repair, circadian regulation, and calcium signaling. Cellular NAD+ concentrations vary by tissue, time of day, and stress exposure. How these consumption pathways interact with redox balance remains an active area of research.
NAD+ is a dinucleotide composed of two nucleotides joined by a pyrophosphate linkage. One nucleotide contains adenine, and the other contains nicotinamide. The oxidized form carries a positive charge on the nicotinamide ring and is abbreviated NAD+. It functions as a cofactor in hydride-transfer reactions, accepting electrons in catabolic pathways. In cells, it interconverts with reduced NADH, forming a redox couple central to energy metabolism. The molecule is water-soluble and does not cross cell membranes freely without specific transport or precursor pathways.
Stability studies show that NAD+ can hydrolyze under prolonged heat, extreme pH, or microbial contamination. Phosphate buffers near neutral pH are often used for short-term handling, though exact stability depends on concentration, temperature, and matrix. In biological samples, endogenous enzymes can rapidly degrade NAD+, making cold chain and fast processing important. Analytical reports should state extraction conditions, internal standards, and validation parameters. Without those details, comparisons across studies remain difficult and potentially misleading.
Laboratory measurement of NAD+ often begins with rapid quenching of cell or tissue samples to prevent enzymatic conversion. Acidic or alkaline extraction can precipitate proteins, but the chosen method affects recovery of oxidized and reduced forms. Enzymatic cycling assays provide high sensitivity by amplifying a NAD+-dependent reaction. High-performance liquid chromatography and mass spectrometry offer separation and structural confirmation. Each method has trade-offs in throughput, specificity, and the ability to distinguish NAD+ from close analogues.
Purified NAD+ is typically supplied as a white to off-white powder and stored desiccated at low temperature. Airtight containers limit moisture uptake, while protection from light reduces degradation of the nicotinamide ring. Aqueous stock solutions are less stable than solid material and are often aliquoted before freezing. Repeated freeze-thaw cycles can lower integrity, so working portions are kept separate. Purity is commonly checked by ultraviolet absorbance near 260 nm, high-performance liquid chromatography, or mass spectrometry.
The stability of NAD+ depends on pH, temperature, light exposure, and the presence of degradative enzymes. Aqueous solutions are generally more stable under mildly acidic to neutral conditions and degrade faster under alkaline conditions or prolonged heat. The solid is hygroscopic and should be stored desiccated, often frozen, and protected from repeated freeze-thaw cycles. In laboratory handling, aliquots reduce repeated temperature changes, and chelating agents may limit metal-catalyzed hydrolysis in some buffers. These practices matter because even small amounts of NADH or hydrolysis products can interfere with quantitative assays.
Quality control for NAD+ materials typically combines identity, purity, and water content checks. Identity may be confirmed by ultraviolet spectrum, retention time in chromatography, or mass accuracy, while purity is assessed by HPLC peak area or quantitative nuclear magnetic resonance. Residual water and solvents can affect molar calculations and enzyme assays, so Karl Fischer titration or thermogravimetric analysis may be used. Commercial materials vary in grade and counterion form, and published methods should specify the exact salt or hydrate when reporting concentrations. Regulatory status depends on intended use, with research reagents, dietary ingredients, and clinical products treated under different frameworks.
Negative selection (background depletion or subtraction) targets and eliminates the host and microbiome genomic background, while aiming to preserve the nucleic acid derived from the pathogens of interest. Degradation of genomic background can be performed through broad-spectrum digestion with nucleases, such as DNase I for DNA background, or by removing abundant RNA species (rRNA, mtRNA, globin mRNA) using sequence-specific RNA depletion kits. Also CRISPR-Cas9-based approaches can be performed to target and deplete human mitochrondrial RNA for example. Generally, however, subtraction approaches lead to a certain degree of loss of the targeted pathogen genome, as poor recovery may occur during the cleanup. Positive enrichment is used to increase pathogen signal rather than reducing background noise. This is commonly done through hybridization-based target capture by probes, which are used to pull out nucleic acid of interest for downstream amplification and sequencing. Panviral probes have been shown to successfully identify diverse types of pathogens in different clinical fluid and respiratory samples, and have been used for sequencing and characterization of novel viruses. However, the probe approach includes extra hybridization and cleanup steps, requiring higher sample input, increasing the risk of losing the target, and increasing the cost and hands-on time. High-throughput sequencing: all the nucleic acids fragments of the library are sequenced.
== Gene expression == The proglucagon gene is expressed in several organs, including the pancreas (α-cells of the islets of Langerhans), gut (intestinal enteroendocrine L-cells) and brain (caudal brainstem and hypothalamus). Pancreatic proglucagon gene expression is promoted upon fasting and hypoglycaemia induction and inhibited by insulin. Conversely, intestinal proglucagon gene expression is reduced during fasting and stimulated upon food consumption. In mammals, the transcription gives rise to identical mRNA in all three cell types, which is further translated to the 180 amino acid precursor called proglucagon. However, as a result of tissue-specific posttranslational processing mechanisms, different peptides are produced in the different cells. In the pancreas (α-cells of the islets of Langerhans), proglucagon is cleaved by prohormone convertase (PC) 2 producing glicentin-related pancreatic peptide (GRPP), glucagon, intervening peptide-1 (IP-1) and major proglucagon fragment (MPGF). In the gut and brain, proglucagon is catalysed by PC 1/3 giving rise to glicentin, which may be further processed to GRPP and oxyntomodulin, GLP-1, intervening peptide-2 (IP-2) and glucagon-like peptide-2 (GLP-2). Initially, GLP-1 was thought to correspond to proglucagon (72–108) suitable with the N-terminal of the MPGF, but sequencing experiments of endogenous GLP-1 revealed a structure corresponding to proglucagon (78–107) from which two discoveries were found. Firstly, the full-length GLP-1 (1–37) was found to be catalysed by endopeptidase to the biologically active GLP-1 (7–37).
A study by Hutchinson and colleagues in 2011 corroborated the previous estimation methods in general, but their estimation of peak growth rates is significantly higher; it found that the "maximum growth rates for T. rex during the exponential stage are 1790 kg/year". Although these results were much higher than previous estimations, the authors noted that these results significantly lowered the great difference between its actual growth rate and the one which would be expected of an animal of its size. The sudden change in growth rate at the end of the growth spurt may indicate physical maturity, a hypothesis which is supported by the discovery of medullary tissue in the femur of a 16 to 20-year-old T. rex from Montana (MOR 1125, also known as B-rex). Medullary tissue is found only in female birds during ovulation, indicating that B-rex was of reproductive age. Further study indicates an age of 18 for this specimen. In 2016, it was finally confirmed by Mary Higby Schweitzer and Lindsay Zanno and colleagues that the soft tissue within the femur of MOR 1125 was medullary tissue. This also confirmed the identity of the specimen as a female. The discovery of medullary bone tissue within Tyrannosaurus may prove valuable in determining the sex of other dinosaur species in future examinations, as the chemical makeup of medullary tissue is unmistakable. Other tyrannosaurids exhibit extremely similar growth curves, although with lower growth rates corresponding to their lower adult sizes.
A 2020 review in The Journal of Bone and Joint Surgery (JB&JS) found it remains broadly popular: ≈2⁄3 of people with OI types III and IV (severe OI) have undergone some form of rodding surgery in their lives, at a mean age of 4+1⁄10 and 7+1⁄2 years respectively; one possible explanation for a tendency towards earlier intervention in type III is that one half of affected children could not walk at all without the surgery, as their limbs were more bowed, so surgery was sought sooner. In those with type III OI who had undergone rodding surgery, 79.5% had the femurs and tibias of both legs rodded. The most common form of rods used are intramedullary (IM) rods, some of which, such as the Fassier–Duval IM rod, are telescoping, meaning that they are designed to grow as the child grows, in an attempt to avoid the necessity of revision surgeries. Telescoping IM rods are widely used, and the common Fassier–Duval IM rod is designed to be used to rod the femur, tibia, and humerus. The surgery involves breaking the long bones in between one and three (or more) places, then fixing the rod alongside the bone to keep it straight. While telescoping IM rods are intended to grow along with both the femur and tibia in developing children; surgeons have a preference to use non-telescoping IM rods, such as Rush rods, in the tibia, which grows less comparatively—the JB&JS review found that while 69.7% of femurs were treated with telescoping IM rods, only 36.9% of tibiae were.
Sources: en.wikipedia.org
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BMS‐986122 is a selective positive allosteric modulator (PAM) of the μ-opioid receptor (MOR). MOR PAMs like BMS-986122 could be useful as novel analgesics with reduced side effects compared to conventional opioid analgesics. However, the potential specifically of BMS-986121 and BMS-986122 as pharmaceutical drugs may be restricted due to their complex synthesis.
=== Healthcare === In order to bridge the gaps in Indian healthcare, Ambani launched the Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute (KDAH) in Mumbai in 2009, a quaternary care facility. It is the only hospital in Mumbai to receive accreditation from the JCI (Joint Commission International, USA), NABH (National Accreditation Board for Healthcare, India), CAP (College of American Pathologists, USA) and NABL (National Accreditation Board for Laboratories, India). Other standouts include the first comprehensive centre for liver transplant and the first integrated centre for children's cardiac care in western India; its robotic surgery programme; the centres for rehabilitation and sports medicine; and its initiative to open 18 cancer care centres in rural Maharashtra.
Sources: en.wikipedia.org
While Fenn was working with Monsanto, the company's research was focused on the production of phosphoric acid and polychlorinated biphenyls (PCBs). Fenn and his colleagues at Monsanto were largely unaware of the health hazards posed by PCBs, indeed because of their inertness, they "practically bathed in the stuff". After spending several more years doing various industrial research, Fenn was looking to get back into the academic world. He had the opportunity to go to Princeton University, where he became the director of Project SQUID. Fenn did not start his Nobel-winning research until later in his career. He was semi-retired when he first published his research on electrospray ionization for mass spectrometry. Fenn felt that his work in electrospray ionization received "a kick in the pants" when proteomics emerged. In 2001, more than 1700 papers on proteomics were published, many using electrospray ionization. Electrospray ionization provides a way to get accurate information about the mass of a large molecule very quickly, even when it is in a mixture of other molecules. The liquid sample is introduced into an electrospray source (at atmospheric pressure) and desolvated with a flow of heated nitrogen gas. This forms small droplets which evaporate in a region under vacuum, which increases the charge on the droplets. For large molecules like proteins, this often results in multiply charge species. Increasing the charge on the molecules, decreased the mass-to-charge ratio, which allows the mass to be more easily determined.
=== Psychiatric disorders === Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from. It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect. Cyproheptadine has been studied for the treatment of post-traumatic stress disorder.
== History == The orexin neuropeptides were discovered in 1998 and the role of the orexin system in the etiology of narcolepsy was identified between 1999 and 2000. Subsequent research further established the role of the orexin system in sleep–wake regulation. Due to the promising potential of orexin system modulation in the treatment of sleep disorders, these findings led to translational efforts to bring orexin receptor modulators to medicine as therapeutic agents. Suvorexant was developed by Merck. It entered clinical development in 2006 and was first described in the medical literature in 2010. The medication was approved by the FDA for the treatment of insomnia in the United States on 13 August 2014. Suvorexant was initially released November 2014 in Japan, then later reached the United States in February 2015, Australia in November 2016, and Canada in November 2018. It was the first orexin receptor antagonist to be introduced for medical use, and was followed by lemborexant in 2019 and daridorexant in 2022. Development of almorexant (ACT-078573) and filorexant (MK-6096) was discontinued, while seltorexant (MIN-202, JNJ-42847922) and vornorexant (ORN-0829, TS-142) are still in clinical trials. Suvorexant marketing exclusivity in the United States was set to expire in January 2023 and patent protection is set to expire in 2029 to 2033.
=== Ownership changes and decline === Shakey Johnson sold his half of the company for $3 million to Colorado Milling and Elevator in 1967, which acquired Plummer's half for $9 million the next year when Colorado Milling merged with Great Western Sugar Company to become Great Western United Corporation. In 1974, Shakey's was sold from Great Western to Hunt International Resources, famous for their attempt to corner the silver market. At the time Hunt International bought Shakey's in 1974, the restaurant chain had approximately 500 stores throughout the United States, including stores as far east as Latham, New York and Westbrook, Maine.
Sources: en.wikipedia.org
It indicates a formal positive charge on the nicotinamide ring. The molecule is not simply a protonated acid, and the charge is part of its redox chemistry.
NAD+ is the oxidized form, while NADH is the reduced form carrying two additional electrons and a proton. The two forms interconvert in many metabolic reactions.
No. NADP+ contains an extra phosphate group on the adenine ribose. NADP+ and NADPH tend to participate in different biosynthetic and antioxidant pathways.
NAD+ and NADH can interconvert quickly after a sample is collected, which can alter the measured ratio. Rapid quenching and cold handling limit enzymatic and chemical changes.