sirtuins comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2026-07-17. Where a claim depends on a specific study, the study is described rather than over-claimed.
Beyond redox chemistry, NAD+ serves as a substrate for enzymes that transfer ADP-ribose or remove acetyl groups. Sirtuins, PARPs, and CD38-family enzymes consume NAD+ and produce nicotinamide and ADP-ribose-related products. These reactions link NAD+ availability to DNA repair, chromatin modification, and cellular signaling. Because the molecule is central to energy metabolism and regulation, changes in its concentration are studied in aging, immunity, and metabolic research. The balance between synthesis and consumption varies by tissue, developmental stage, and physiological state.
In humans, NAD+ can be synthesized from nicotinic acid, nicotinamide, nicotinamide riboside, and tryptophan through overlapping pathways. The salvage pathway recycles nicotinamide back to NAD+ and is often considered a major route in many tissues. Dietary precursors and intracellular recycling both contribute to the pool, but the quantitative importance of each source remains an active research question. NAD+ levels are not uniform across organs or cell compartments. Measurements in blood do not necessarily reflect concentrations inside tissues.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common name | Nicotinamide adenine dinucleotide (oxidized) | Often shortened to NAD+ |
| Chemical class | Dinucleotide | Contains nicotinamide and adenine moieties |
| Molecular formula | C21H27N7O14P2 | Free acid form; charge depends on pH |
| Molar mass | About 663.43 g/mol | Calculated for C21H27N7O14P2 |
| CAS number | 53-84-9 | Common identifier for beta-NAD+ |
Stability of NAD+ depends on form, temperature, pH, and water content. The solid is generally more stable than solutions, and it should be kept dry and cold. In solution, hydrolysis can cleave the dinucleotide, especially under alkaline conditions or at elevated temperature. Light exposure may also contribute to degradation. Buffers, chelating agents, and sterile handling can reduce losses, but no single condition preserves all preparations indefinitely. Researchers often prepare working solutions shortly before use and verify activity or purity after storage.
Quality control for NAD+ relies on identity, purity, and functional tests. A certificate of analysis may report high-performance liquid chromatography purity, ultraviolet spectrum, water content, and residual solvents. Because NAD+ is hygroscopic, gravimetric values can shift as material absorbs water, so purity should be interpreted alongside storage history. Mass spectrometry confirms molecular identity, while enzymatic assays show whether the material supports dehydrogenase activity. Commercial material is available as the free acid and as salts, and the counterion affects molecular weight, solubility, and how concentrations are calculated.
Laboratory measurement of NAD+ usually begins with rapid sample quenching because the molecule can change form after collection. Enzymatic cycling assays amplify signal through coupled reactions and are suited to small samples. High-performance liquid chromatography with ultraviolet detection separates NAD+ from related nucleotides. Liquid chromatography-mass spectrometry offers higher specificity and can distinguish NAD+ from close analogs. Each method has trade-offs in sensitivity, throughput, and equipment needs, so reported values depend heavily on extraction and detection choices.
NAD+ is a dinucleotide composed of adenine, ribose, and nicotinamide groups joined by phosphate linkages. It serves as a coenzyme in oxidoreductase reactions, cycling between oxidized NAD+ and reduced NADH. The molecule is water-soluble and occurs in all living cells. Its nicotinamide ring accepts hydride ions during catabolic reactions, linking substrate oxidation to electron transport. This redox couple supports ATP production and helps maintain cytosolic and mitochondrial redox balance in many cell types.
Beyond redox catalysis, NAD+ is a substrate for enzymes that transfer ADP-ribose or remove acetyl groups from proteins. Sirtuins and poly(ADP-ribose) polymerases consume NAD+ and release nicotinamide as a byproduct. These reactions connect cellular energy status to gene regulation, DNA repair, and stress responses. Because NAD+ is used rather than merely recycled in such signaling, its concentration reflects both biosynthesis and consumption. The balance between salvage and de novo synthesis pathways determines available pools in different tissues.
Biosynthesis of NAD+ starts from nicotinamide, nicotinic acid, or nicotinamide riboside through salvage pathways. A rate-limiting enzyme, nicotinamide phosphoribosyltransferase, converts nicotinamide to nicotinamide mononucleotide. Further coupling with ATP yields NAD+. In mammals, the liver and muscle can synthesize NAD+ from dietary precursors, but tissue levels vary widely. Researchers study these pathways to understand age-related changes, metabolic disorders, and neurodegeneration. Direct causal links between NAD+ decline and disease remain an active area of investigation.
Nicotinamide adenine dinucleotide, commonly abbreviated NAD+, is a coenzyme present in all living cells. The molecule consists of two nucleotides linked by phosphate groups, with adenine and a nicotinamide ring as its principal features. In its oxidized form, the nicotinamide ring can accept a hydride ion, becoming NADH. This reversible conversion places NAD+ at the center of many electron-transfer reactions. Its role as a redox carrier is well established across bacteria, plants, fungi, and animals.
Beyond redox chemistry, NAD+ acts as a substrate for several enzyme families. ADP-ribosyltransferases, sirtuins, and CD38 ectoenzymes cleave the molecule into nicotinamide and ADP-ribose or related products. These reactions connect NAD+ availability to processes such as DNA repair, chromatin modification, and calcium signaling. Because the coenzyme is used in both electron transfer and signaling, cells maintain separate pools in compartments including the cytosol, mitochondria, and nucleus. The relative sizes and regulation of those pools remain active areas of study.
Cells produce NAD+ through several biosynthetic routes. The salvage pathway recycles nicotinamide, while the Preiss-Handler pathway uses nicotinic acid, and a de novo route can start from tryptophan in some organisms. In mammals, the salvage pathway is generally considered the main source under ordinary conditions. Tissue concentrations vary widely by cell type and compartment, and measured declines with age have been reported in some studies. Whether such changes drive aging or mainly accompany it remains an open question.
== Honours and awards == In the 2020 New Year Honours, Heffernan was appointed a Companion of the New Zealand Order of Merit, for services to health. On her appointment, Heffernan asked New Zealanders to play their part to reduce antibiotic resistance, saying, "While antibiotics are essential medicines to treat bacterial infections, we overuse and misuse them and this contributes to resistance". On her retirement in 2018, after a 43-year career, ESR awarded Heffernan their Lifetime Achievement Award.
SeV has been known to the research community since the late 1950s and has been widely used to create numerous variants of genetically engineered constructs, including vectors for transgene delivery. Creation of SeV genetic constructs is easier compared to other viruses, many SeV genes have a transcriptional initiation and termination signals. Therefore, constructing a recombinant virus is straightforward; the foreign gene can be introduced into the viral genome by replacing or adding viral protein expressing gene(s). SeV can include a foreign gene or even multiple genes of large size. It has been demonstrated that a gene of more than 3 kb can be inserted and expressed in SeV. Due to exclusively cytoplasmic replication, the virus does not carry the risk of genetic integration into the host genomes, which is a problem for many other viral vectors. The genome of SeV as genomes of other non segmented negative-stranded RNA viruses has a low rate of homologous recombination and evolves comparatively slowly. Multiple reasons for this genomic stability exist: (1) the genome is nonsegmented, therefore cannot undergo genetic reassortment, (2) each protein and each amino acid has an important function. Therefore, any new genetic insertion, substitution or deletion would lead to a decrease or total loss of function that would in turn cause the new virus variant to be less viable. (3) Sendai virus belongs to a category of viruses that are governed by the "rule of six". SeV genome as genomes of other paramyxoviruses mainly include six genes, which encode for six major proteins.
The environment of the migrating cell can affect its speed, persistence and direction of migration by stimulating it. The extracellular matrix (ECM) provides not only the structural and biochemical support, but also plays a major role in regulating cell behavior. Different ECM proteins (such as collagen, elastin, fibronectin, laminin, and others) allow cells to adhere and migrate, while forming focal adhesions in the front and disassembling them in the back. Using these adhesion sites, cells also sense the mechanical properties of the ECM. Cells can be guided by a gradient of those proteins (haptotaxis) or a gradient of soluble substrates in the liquid phase surrounding the cell (chemotaxis). Cells sense the substrate through their receptors and migrate toward the concentration (or the opposite direction). Another form of stimulation can be rigidity gradients of the ECM (durotaxis).
Sources: en.wikipedia.org
=== 2020s === 2020: The Nigerian Academy of Science elected epidemiologist/parasitologist Ekanem Braide as its first female president. 2020: Brazilian Scientist and Researcher Jaqueline Goes de Jesus, sequenced COVID-19 genome in 12 hours. 2020: Biochemists Jennifer Doudna (American) and Emmanuelle Charpentier (French) received the Nobel Prize in Chemistry for their work on CRISPR genome editing tool. 2020: American astronomer Andrea M. Ghez received the Nobel Prize in Physics for the discovery of a supermassive compact object. 2020: German-Turkish scientist Özlem Türeci is the co-founder and chief medical officer of BioNTech. Her team developed BNT162b2 (tozinameran (INN)), commonly known as the Pfizer–BioNTech COVID-19 vaccine. 2020: British vaccinologist Sarah Gilbert leads the development and testing of a vaccine which becomes the Oxford–AstraZeneca COVID-19 vaccine. 2021: Catherine Heymans was appointed as the first female Astronomer Royal for Scotland. 2022: American chemist Carolyn R. Bertozzi received the Nobel Prize in Chemistry for her development of Bioorthogonal chemistry. 2023: Australian geomicrobiologist Jillian Banfield became the first female recipient of the van Leeuwenhoek Medal, which she received for her studies of complex microbial communities and their interaction with the environment. 2023: Hungarian American scientist Katalin Kariko receives Noble prize in Physiology or Medicine with Drew Weissman for their discoveries on nucleoside base modifications that enabled the development of effective mRNA vaccines.
== Killing == Around 9 a.m. on November 20, 1932, Robert Karriem had escorted James J. Smith into a room with a makeshift altar in the home at 1429 DuBois Street. Robert Karriem was described as a large 44 year old negro who had moved from Tennessee to Detroit on July 3, 1929. Smith, 40, was described as a negro. In the audience were twelve adult witnesses and Karriem's wife and children. Smith was asked if he would sacrifice his life for Islam, and Smith nodded his assent. Karriem then stabbed Smith in the chest, and proceeded to bludgeon him to death with an axle rod. Smith's body was found on the altar, stabbed through the chest with an 8-inch knife. A "cheap magazine" was open to a story about "mysticism of the desert", with the underlined phrase "The believer must be stabbed through the heart".
Glutathione S-transferase theta-1 is an enzyme that in humans is encoded by the GSTT1 gene. Glutathione S-transferase (GST) theta 1 (GSTT1) is a member of a superfamily of proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. Human GSTs can be divided into five main classes: alpha, mu, pi, theta, and zeta. The theta class includes GSTT1 and GSTT2. The GSTT1 and GSTT2 share 55% amino acid sequence identity and both of them were claimed to have an important role in human carcinogenesis. The GSTT1 gene is located approximately 50kb away from the GSTT2 gene. The GSTT1 and GSTT2 genes have a similar structure, being composed of five exons with identical exon/intron boundaries.
The GABAA receptor agonist gaboxadol (THIP; LU-2-030), a synthetic derivative of the neurotransmitter γ-aminobutyric acid (GABA) and an analogue of the alkaloid muscimol, underwent formal clinical development for the treatment of insomnia and reached phase 3 clinical trials for this indication in the 1990s and 2000s. It was found to effectively improve sleep onset and duration in people with insomnia. In addition, and unlike other hypnotics like benzodiazepines, gaboxadol improved slow wave sleep, preserved sleep architecture, and did not suppress REM sleep. Moreover, in contrast to benzodiazepines, tolerance did not appear to develop to gaboxadol's hypnotic effects. The development of gaboxadol was discontinued in 2007. This was due to high rates of psychiatric and hallucinogenic effects in drug users at supratherapeutic doses, failure of a 3-month efficacy trial, and other cited reasons. Moreover, there was tension concerning hypnotics in the pharmaceutical industry at the time owing to bizarre reports of zolpidem (Ambien)-induced delirium that emerged in the media in 2006, which may have made the developer of gaboxadol more concerned about potential liability issues. According to journalist Hamilton Morris, the discontinuation of gaboxadol's late-stage development may have deprived people with insomnia access to an effective, safe, and non-addictive treatment. There has been some further study of gaboxadol as a hypnotic by David Nutt and colleagues following the discontinuation of its development.
Sources: en.wikipedia.org
The plus sign indicates the oxidized form of nicotinamide adenine dinucleotide, which can accept electrons. When it accepts electrons, it becomes NADH. The two forms together support redox reactions in cells.
No. NAD+ is the oxidized form and NADH is the reduced form. They differ by two electrons and a proton equivalent, and cells interconvert them during metabolism.
Yes. NAD+ is present in all living cells and is required for fundamental metabolic reactions. Its concentration varies by tissue, compartment, and time.
NAD+ is the oxidized form, while NADH is the reduced form carrying an added hydride. The two form a redox pair that cells use in many energy-yielding reactions.