If you have been reading about Sirtuin substrate and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-05-10. Where a claim depends on a specific study, the study is described rather than over-claimed.
NAD+ is a dinucleotide composed of nicotinamide, ribose, and adenine linked by phosphate groups. Its full name is nicotinamide adenine dinucleotide, with "+" denoting the oxidized form. The molecule acts as a coenzyme in redox reactions, cycling between NAD+ and NADH. In cells, it participates in electron transfer during glycolysis, the citric acid cycle, and oxidative phosphorylation. It is distinct from NADP+, which carries an additional phosphate group and supports different biosynthetic reactions.
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.
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.
Related compounds include NADH, the reduced form, and NADP+, which carries an additional phosphate group. NADP+ and NADPH often serve in biosynthetic and antioxidant reactions, while NAD+ and NADH are more associated with energy-yielding catabolism. Nicotinamide, nicotinic acid, and nicotinamide riboside are precursors that can enter salvage pathways. The exact contribution of dietary precursors to tissue NAD+ pools is an area of active investigation. Some studies measure labeled precursors to trace those routes.
| 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+ |
Nicotinamide adenine dinucleotide, commonly abbreviated NAD+, is a dinucleotide coenzyme built from an adenine nucleotide and a nicotinamide nucleotide joined by a pyrophosphate linkage. Its oxidized form carries a positive charge on the nicotinamide ring, while the reduced form, NADH, carries a hydride equivalent. The molecule participates in hundreds of oxidoreductase reactions, where it accepts or donates electrons and protons. Because it can cycle between oxidized and reduced states without net consumption, NAD+ functions as a reusable electron carrier rather than a fuel molecule.
In glycolysis, the tricarboxylic acid cycle, and fatty acid oxidation, NAD+ is reduced to NADH at specific dehydrogenase steps. NADH then delivers electrons to the mitochondrial electron transport chain, mainly at complex I, supporting oxidative phosphorylation and ATP production. The balance between NAD+ and NADH, often expressed as a ratio, influences metabolic flux and redox homeostasis in different cellular compartments. Cytosolic and mitochondrial pools are connected but not identical, and their ratios can differ substantially because of compartment-specific enzymes and transport systems.
Beyond redox chemistry, NAD+ serves as a substrate for enzymes that cleave the molecule and transfer its ADP-ribose moiety or remove acetyl groups. Sirtuins consume NAD+ during deacetylation, poly(ADP-ribose) polymerases use it in DNA damage responses, and CD38 enzymes hydrolyze it to signaling metabolites. These consumption pathways mean that NAD+ availability can influence gene regulation, DNA repair, and calcium signaling. Cellular NAD+ concentrations decline in some tissues with age in animal models, but whether this decline is a cause or consequence of aging in humans remains an active open question.
Solid NAD+ is relatively stable when kept dry, cold, and protected from light. Aqueous solutions are more vulnerable to hydrolysis and can lose activity during repeated freeze-thaw cycles or prolonged storage at ambient temperature. Stability depends on pH, ionic strength, and the presence of degrading enzymes or metal ions. For many laboratory uses, aliquots are stored frozen and thawed only once. Exact degradation rates vary by matrix, so stability should be checked for each application rather than assumed.
Laboratory handling of NAD+ follows standard practices for hygroscopic fine chemicals. Personnel typically avoid inhalation and skin contact, use gloves and eye protection, and work in a ventilated area. Quality control may include ultraviolet absorbance at the nicotinamide maximum, chromatographic purity, water content, and identity confirmation by mass spectrometry. Because commercial preparations can contain counterions, residual solvents, or related nucleotides, a certificate of analysis helps verify the material. Researchers should confirm that the form supplied matches the intended assay.
Measuring NAD+ in biological samples requires care because the molecule is chemically reactive and present at low concentrations in some tissues. Common approaches include enzymatic cycling assays, high-performance liquid chromatography, and liquid chromatography coupled to mass spectrometry. Each method has different sensitivity and specificity, and sample preparation can affect results. Acidic or alkaline extraction steps are used in some protocols, but the choice depends on the analyte and matrix. No single method is universally optimal for every tissue or fluid.
=== Plasma fractionation and Wiener directorship === In 1952, operation commenced plasma fractionation. Thereafter the range of antivenoms increased, including those against other snake species such as death adder (Acanthophis antarcticus) and the taipan (Oxyuranus scutellatus), plus spiders including the redback (Latrodectus hasselti) and – after much difficulty – the Sydney funnel-web (Atrax robustus). Much of this work, including the introduction in 1962 of a polyvalent antivenom against all of the major terrestrial Australian snakes, occurred under the direction of Saul Wiener, while from 1966 until the mid-1990s, venom research was coordinated by the eccentric but dedicated Struan Sutherland, who in 1979 released new guidelines for snakebite first aid, and a new test for snakebites that would identify which snake had envenomated the victim. Other major achievements of CSL include:
In modern Europe and North America, ayahuasca analogues (i.e., variants) are often prepared using non-traditional plants which contain the same alkaloids. For example, seeds of the Syrian rue plant can be used as a substitute for the ayahuasca vine, and the DMT-rich Mimosa hostilis is used in place of chacruna. Australia has several indigenous plants which are popular among modern ayahuasqueros there, such as various DMT-rich species of Acacia. The name "ayahuasca" specifically refers to a decoction that contains Banisteriopsis caapi. Brews similar to ayahuasca may be prepared using several plants not traditionally used in South America: DMT admixtures:
In May 2007, Unilever became the first company to commit to sourcing all tea in a sustainable manner. Working with the Rainforest Alliance, an international environmental NGO, Unilever, announced all Lipton Yellow Label tea bags sold in Western Europe would be certified by 2010 and all Lipton tea bags sold globally by 2015. Lipton's own tea estates were among the first to be certified. Lipton tea bearing the Rainforest Alliance seal appeared on Western European markets in 2008 and started appearing in North America in 2009. On 6 May 2009, Lipton received a Corporate Green Globe Award for its work with the Rainforest Alliance. In 2011, PETA criticized Unilever for conducting and funding experiments on rabbits, pigs and other animals in an attempt to make human health claims about the tea's ingredients. According to the animal rights organization, Unilever decided to end the practice after receiving more than 40,000 appeals from PETA supporters and days before PETA made plans to launch its "Lipton CruelTEA" campaign. Unilever no longer tests their products on animals unless required to by governments as part of their regulatory requirements. Unilever reached an agreement in November 2021 to sell the majority of its tea business to private equity firm CVC Capital Partners for €4.5 billion. This included the Lipton brand except where Unilever retained its use for tea in India, Nepal, and Indonesia, for ready to drink teas globally, and for soup mixes in North America. The sale was completed in July 2022, with the new company named ‘Lipton Teas and Infusions’.
=== Photography === In photography, formaldehyde is used in low concentrations for the process C-41 (color negative film) stabilizer in the final wash step, as well as in the process E-6 pre-bleach step, to make it unnecessary in the final wash. Due to improvements in dye coupler chemistry, more modern (2006 or later) E-6 and C-41 films do not need formaldehyde, as their dyes are already stable.
Sources: en.wikipedia.org
=== Other === Labial fusion, also called labial adhesion, is the fusion of the labia minora. This affects a number of young girls and is not considered unduly problematic. The condition can usually be treated using creams, or it may right itself with the release of hormones at the onset of puberty. Clitoromegaly is an enlarged clitoris caused by either anabolic steroids or an intersex condition. Vulvodynia is chronic pain in the vulvar region. There is no single identifiable cause. A subtype of this is vulvar vestibulitis but since this is not thought to be an inflammatory condition it is more usually referred to as vestibulodynia. Vulvar vestibulitis usually affects pre-menopausal women. Pudendal nerve entrapment can cause sharp pain or numbness in the vulva. This condition can be caused by activities such as cycling, giving birth, or prolonged sitting. A number of skin disorders such as lichen sclerosus, and lichen simplex chronicus can affect the vulva. Crohn's disease of the vulva is an uncommon form of metastatic Crohn's disease, which manifests as a skin condition showing as hypertrophic lesions or vulvar abscesses. Papillary hidradenomas are nodules that can ulcerate and are mostly found on the skin of the labia or of the interlabial folds. Another more complex ulcerative condition is hidradenitis suppurativa, which is characterised by painful cysts that can ulcerate, and recur, and can become chronic lasting for many years. Chronic cases can develop into squamous cell carcinomas.
== Further reading == Ghelardini, C.; Galeotti, N.; Di Cesare Mannelli, L.; Mazzanti, G.; Bartolini, A. (2001). "Local anaesthetic activity of beta-caryophyllene". Farmaco. 56 (5–7): 387–389. doi:10.1016/S0014-827X(01)01092-8. hdl:2158/397975. PMID 11482764.
Colombia, officially the Republic of Colombia, is a country located in South America, with insular regions in North America. Colombia's mainland is bordered by the Caribbean Sea to the north, Venezuela to the east, Brazil to the southeast, Peru and Ecuador to the south and southwest, the Pacific Ocean to the west, and Panama to the northwest. Colombia is divided into 32 departments. The Capital District of Bogotá is the country's largest city hosting the main financial and cultural hub. Other urban areas include Medellín, Cali, Barranquilla, Cartagena, Bucaramanga, Pereira, Santa Marta, Cúcuta, Ibagué, Villavicencio and Manizales. It covers an area of 1,141,748 square kilometers (440,831 sq mi) and has a population of around 52 million. Its rich cultural heritage—including language, religion, cuisine, and art—reflects its history as a colony, fusing cultural elements brought by immigration from Europe and the Middle East, with those brought by the African diaspora, as well as with those of Indigenous civilizations that predate colonization. Spanish is the official language, although Creole, English and 64 other languages are recognized regionally. Colombia has been home to many Indigenous peoples and cultures since at least 12,000 BCE. The Spanish landed in La Guajira in 1499, and by the mid-16th century had colonized much of present-day Colombia, establishing the New Kingdom of Granada. Independence from the Spanish Empire was declared in 1810, with what is now Colombia emerging as the United Provinces of New Granada.
Sources: en.wikipedia.org
Dehydrogenation by 17β-hydroxysteroid dehydrogenase (17β-HSD) into estrone Conjugation by estrogen sulfotransferases and UDP-glucuronyltransferases into C3 and/or C17β estrogen conjugates like estrone sulfate and estradiol glucuronide Hydroxylation by cytochrome P450 enzymes such as CYP1A1 and CYP3A4 into catechol estrogens like 2-hydroxyestrone and 2-hydroxyestradiol as well as 16-hydroxylated estrogens like 16α-hydroxyestrone and estriol (16α-hydroxyestradiol) The liver is almost entirely responsible for metabolism of estradiol. Both dehydrogenation of estradiol by 17β-HSD into estrone and conjugation into estrogen conjugates are reversible transformations. However, in regards to sulfation and desulfation, transformation of estrone into estrone sulfate is predominant relative to the reverse reaction. Estradiol can also be reversibly converted into long-lived lipoidal estradiol forms like estradiol palmitate and estradiol stearate as a minor route of metabolism. The elimination half-life of estradiol administered via intravenous injection has been found to be 2 hours in men and 27 to 50 minutes in women. Other routes of administration of estradiol like oral administration or intramuscular injection have far longer elimination half-lives and durations of action due to (1) the formation of a large circulating reservoir of metabolism-resistant estrogen conjugates that can be reconverted back into estradiol and/or (2) the formation of slowly-releasing depots.
=== In plants === Plant synthesis of vitamin B6 contributes to protection from sunlight. Ultraviolet-B radiation (UV-B) from sunlight stimulates plant growth, but in high amounts can increase production of tissue-damaging reactive oxygen species (ROS), i.e., oxidants. Using Arabidopsis thaliana (common name: thale cress), researchers demonstrated that UV-B exposure increased pyridoxine biosynthesis, but in a mutant variety, pyridoxine biosynthesis capacity was not inducible, and as a consequence, ROS levels, lipid peroxidation, and cell proteins associated with tissue damage were all elevated. Biosynthesis of chlorophyll depends on aminolevulinic acid synthase, a PLP-dependent enzyme that uses succinyl-CoA and glycine to generate aminolevulinic acid, a chlorophyll precursor. In addition, plant mutants with severely limited capacity to synthesize vitamin B6 have stunted root growth, because synthesis of plant hormones such as auxin require the vitamin as an enzyme cofactor.
== History == The law was named after scientist Jacques Charles, who formulated the original law in his unpublished work from the 1780s. In two of a series of four essays presented between 2 and 30 October 1801, John Dalton demonstrated by experiment that all the gases and vapours that he studied expanded by the same amount between two fixed points of temperature. The French natural philosopher Joseph Louis Gay-Lussac confirmed the discovery in a presentation to the French National Institute on 31 Jan 1802, although he credited the discovery to unpublished work from the 1780s by Jacques Charles. The basic principles had already been described by Guillaume Amontons and Francis Hauksbee a century earlier. Dalton was the first to demonstrate that the law applied generally to all gases, and to the vapours of volatile liquids if the temperature was well above the boiling point. Gay-Lussac concurred. With measurements only at the two thermometric fixed points of water (0°C and 100°C), Gay-Lussac was unable to show that the equation relating volume to temperature was a linear function. On mathematical grounds alone, Gay-Lussac's paper does not permit the assignment of any law stating the linear relation. Both Dalton's and Gay-Lussac's main conclusions can be expressed mathematically as:
The concentration of secondary metabolites such as phenylpropanoids and flavonoids can also be altered in plants exposed to high concentrations of CO2. Plants also emit CO2 during respiration, and so the majority of plants and algae, which use C3 photosynthesis, are only net absorbers during the day. Though a growing forest will absorb many tons of CO2 each year, a mature forest will produce as much CO2 from respiration and decomposition of dead specimens (e.g., fallen branches) as is used in photosynthesis in growing plants. Contrary to the long-standing view that they are carbon neutral, mature forests can continue to accumulate carbon and remain valuable carbon sinks, helping to maintain the carbon balance of Earth's atmosphere. Additionally, and crucially to life on earth, photosynthesis by phytoplankton consumes dissolved CO2 in the upper ocean and thereby promotes the absorption of CO2 from the atmosphere.
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.
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.