Everything below concerns redox coenzyme. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-12-06. Numbers and descriptions here follow the published literature rather than marketing material.
Nicotinamide adenine dinucleotide, abbreviated NAD+, is a dinucleotide built from adenine, nicotinamide, two ribose sugars, and two phosphate groups. The oxidized form carries a positive charge on the nicotinamide ring, while the reduced form, NADH, is neutral. This pair acts as a reversible electron carrier in cells. NAD+ is present in bacteria, plants, animals, and fungi. Its structure allows it to accept and donate electrons without being consumed in the reactions it supports.
In redox reactions, NAD+ accepts a hydride ion, which consists of two electrons and one proton. The hydride adds to the nicotinamide ring at a specific carbon, converting NAD+ into NADH. Dehydrogenase enzymes use this step in glycolysis, the citric acid cycle, and fatty acid oxidation. NADH later donates electrons to the mitochondrial electron transport chain, helping to drive ATP synthesis. The balance between NAD+ and NADH reflects the metabolic state of a cell, and shifts in that balance can alter how pathways operate.
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.
| Property | Value | Notes |
|---|---|---|
| Molar mass | 663.43 g/mol | For the free acid form; salts have higher mass. |
| Appearance | White to off-white powder | Often hygroscopic; may clump on exposure to air. |
| Solubility | Freely soluble in water | Poorly soluble in nonpolar organic solvents. |
| Typical storage | -20 °C, desiccated | Protect from light and moisture; avoid repeated freeze-thaw. |
| Common synonyms | beta-NAD, DPN | DPN stands for diphosphopyridine nucleotide, an older name. |
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.
Measuring NAD+ in biological samples requires rapid processing because the compound can degrade or interconvert after collection. Common approaches include enzymatic cycling assays, high-performance liquid chromatography, and mass spectrometry. Each method has different sensitivity, specificity, and susceptibility to interference from related nucleotides. Sample type matters: cultured cells, animal tissues, and human blood present distinct challenges. Reported values can vary widely across laboratories because of differences in extraction, normalization, and analytical platform. Standardization remains an open issue in the field.
NAD+ is relatively unstable in aqueous solution, especially at neutral or alkaline pH and at elevated temperatures. It is typically stored dry, protected from light and moisture, and kept cold or frozen for long-term use. Solutions are often prepared fresh or buffered to mildly acidic pH to slow hydrolysis. Repeated freeze-thaw cycles can reduce integrity. Laboratories may verify concentration using ultraviolet absorbance at 259 nm or by enzymatic assay. These handling practices are general laboratory conventions rather than universal rules.
Research on NAD+ often examines changes with age, diet, exercise, and disease states, but causal relationships are difficult to establish. Some studies measure NAD+ levels, while others assess enzyme activity or downstream markers. In the literature, terms such as "NAD+ decline" and "NAD+ boosting" appear in both scientific and commercial contexts, sometimes without precise definitions. Whether changes in measured NAD+ directly produce health effects remains an open question. Results from cells, animals, and humans cannot be assumed to translate directly.
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.
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.
Commercial NAD+ is available at research grade, often with purity specifications determined by high-performance liquid chromatography. Certificates of analysis may report water content, residual solvents, and counterion identity. Identity can be confirmed by ultraviolet absorbance near 260 nm, mass spectrometry, or enzymatic activity. Because different salt forms and hydration states exist, researchers should verify that the product matches the intended molecular form. Lot-to-lot variation in purity can affect quantitative assays and should be documented.
Solid NAD+ is usually supplied as a white to off-white powder or lyophilized preparation. It is hygroscopic and should be kept desiccated at low temperature, commonly -20 °C or below for long-term storage. Aqueous solutions are less stable than dry material and are often prepared fresh or stored frozen in aliquots. Light exposure and repeated freeze-thaw cycles can promote degradation, so amber containers and single-use aliquots are preferred. Buffered solutions near neutral pH are generally less stable than acidic or frozen preparations.
Quantification of NAD+ in biological samples typically uses liquid chromatography coupled to mass spectrometry. Enzymatic cycling assays offer higher throughput and rely on NAD+ dependent dehydrogenases to amplify signal. Both approaches require careful sample quenching because NAD+ can be rapidly consumed or converted after collection. Acidic extraction is common for NAD+, while alkaline conditions favor NADH in some protocols. Isotopically labeled internal standards help correct for losses during extraction and ionization.
Measurement of total bilirubin includes both unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named UDP-glucuronyl-transferase. When the total bilirubin level exceeds 17 μmol/L, it indicates liver disease. When total bilirubin levels exceed 40 μmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called jaundice. The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a haematoma and ineffective erythropoiesis leading to increased red blood cell destruction. Gilbert's syndrome and Crigler–Najjar syndrome have defects in the UDP-glucuronyl-transferase enzyme, affecting bilirubin conjugation. The degree of rise in conjugated bilirubin is directly proportional to the degree of hepatocyte injury. Viral hepatitis can also cause the rise in conjugated bilirubin. In parenchymal liver disease and incomplete extrahepatic obstruction, the rise in conjugated bilirubin is less than the complete common bile duct obstruction due to malignant causes. In Dubin–Johnson syndrome, a mutation in multiple drug-resistance protein 2 (MRP2) causes a rise in conjugated bilirubin.
RNA, in contrast, forms large and complex 3D tertiary structures reminiscent of proteins, as well as the loose single strands with locally folded regions that constitute messenger RNA molecules. Those RNA structures contain many stretches of A-form double helix, connected into definite 3D arrangements by single-stranded loops, bulges, and junctions. Examples are tRNA, ribosomes, ribozymes, and riboswitches. These complex structures are facilitated by the fact that RNA backbone has less local flexibility than DNA but a large set of distinct conformations, apparently because of both positive and negative interactions of the extra OH on the ribose. Structured RNA molecules can do highly specific binding of other molecules and can themselves be recognized specifically; in addition, they can perform enzymatic catalysis (when they are known as "ribozymes", as initially discovered by Tom Cech and colleagues).
Recent evidence has suggested that this macrophage activation may involve a phenomenon known as innate immune memory. Also known as trained immunity, innate immune memory is the innate immune system's ability, upon exposure to oxLDL or other atherogenic stimuli, to undergo epigenetic and metabolic reprogramming, leading to a hyperaugmented immune response following a secondary, non-specific restimulation. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die and further propagate the inflammatory process. In addition to these cellular activities, there is also smooth muscle proliferation and migration from the tunica media into the intima in response to cytokines secreted by damaged endothelial cells. This leads to the formation of a fibrous capsule covering the fatty streak. Intact endothelium can prevent this smooth muscle proliferation by releasing nitric oxide.
Sources: en.wikipedia.org
Kecap manis: Sweetened soy sauce, which has a thick syrupy consistency and a unique, pronounced, sweet, somewhat treacle-like flavor due to generous addition of palm sugar. Regular soy with brown sugar and a trace of molasses added can substitute. It is by far the most popular type of soy sauce employed in Indonesian cuisine, accounts for an estimated 90 percent of the nation's total soy sauce production. Kecap manis is an important sauce in Indonesian signature dishes, such as nasi goreng, mie goreng, satay, tongseng and semur. Sambal kecap for example is type of sambal dipping sauce of kecap manis with sliced chili, tomato and shallot, a popular dipping sauce for sate kambing (goat meat satay) and ikan bakar (grilled fish/seafood). Since soy sauce is of Chinese origin, kecap asin is also an important seasoning in Chinese Indonesian cuisine. Kecap manis sedang: Medium sweet soy sauce, which has a less thick consistency, is less sweet and has a saltier taste than kecap manis. Kecap asin: Regular soy sauce derived from the Japanese shoyu, but usually more concentrated and thicker, with a darker color and stronger flavor; it can be replaced by Chinese light soy sauce in some recipes. Salty soy sauce was first introduced into Indonesia by Hokkien people so its taste resembles that of Chinese soy sauce. Hakka soy sauce made from black beans is very salty and large productions are mainly made in Bangka Island.
== Toponym == The name of the town was attested in 1489, even before it was founded by François I in the form le Hable de Grace then Ville de Grace in 1516, two years before its official founding. The learned and transient name of Franciscopolis in tribute to the same king, is encountered in some documents then that of Havre Marat, referring to Jean-Paul Marat during the French Revolution but was not imposed. However it explains why the complementary determinant -de-Grace was not restored. This qualifier undoubtedly referred to the Chapel of Notre Dame located at the site of the cathedral of the same name. The chapel faced the Chapel Notre Dame de Grace of Honfleur across the estuary. The common noun havre meaning 'port' was out of use at the end of the 18th or beginning of the 19th centuries but is still preserved in the phrase havre de paix meaning 'safe haven'. It is generally considered a loan from Middle Dutch from the 12th century. A Germanic origin can explain the "aspiration" of the initial h. Havre de Grace, Maryland, in the United States retains the de Grace from colonial times. New research however focuses on the fact that the term was attested very early (12th century) and in Norman texts in the forms Hable, hafne, havene, havne, and haule makes a Dutch origin unlikely.
=== Stress-responsive kinases === Kinases that regulate p53 phosphorylation can be divided into two broad groups. One group includes members of the MAPK pathways, including JNK1–3, ERK1/2 and p38 MAPK, which are activated by diverse cellular stresses such as oxidative stress and heat shock. A second group comprises DNA damage response kinases, including ATM, ATR and DNA-PK, together with downstream checkpoint kinases such as CHK1 and CHK2, which are activated by DNA damage and replication stress and contribute to p53 regulation through phosphorylation-dependent signalling. Additional kinases implicated in p53 phosphorylation include the CDK-activating kinase (CAK; CDK7–cyclin H–MAT1), which has been shown to phosphorylate p53 (for example at Ser33) in vitro and in vivo, and TP53RK (PRPK), which has been reported to phosphorylate p53 at Ser15. Oncogene-induced activation of p53 can also occur via p14ARF (ARF), which inhibits the p53 antagonist MDM2 and thereby stabilizes p53.
== Other animals == Extensive comparative anatomy work has been done to study the evolution of pancreatic islets across representatives of all major groups of vertebrates and a number of different invertebrates. Islet organs are absent in any invertebrate and primitive chordates (tunicates and lancelets). During the evolution of vertebrates, the cell types secreting peptides related to insulin, somatostatin, glucagon, and PP moved from the brain to the gastrointestinal track mucosa (insulin first in tunicates, all four in lancelets), and then migrated out sequentially to form an islet structure (insulin and somatostatin first in jawless fish, followed by glucagon in jawed cartilaginous fish, few or no PP in lobe-finned bony fish, numerous PP in some ray-finned bony fish, ghrelin detected in catfish). In birds, other peptide-secreting cells such as IGF-1, PYY, and adrenomedullin have been localized in the islets. Notably, American anglerfish pancreas — unlike those of mammals — has islets that are rich in endocrine cells and mostly free of pancreatic exocrine tissue, making them ideal sources of endocrine cells for research. It eventually enabled the isolation of the cDNA for preproglucagon, which contained the sequence for glucagon and two other glucagon-like peptides (GLP-1 and GLP-2).
Sources: en.wikipedia.org
It indicates the oxidized form, which has a positive charge on the nicotinamide nitrogen. The reduced partner NADH lacks that charge and carries added electrons. The plus sign is part of the standard abbreviation, not a separate ion.
No. It also serves as a substrate for signaling and DNA-repair enzymes such as sirtuins and PARPs. Those reactions consume NAD+ and connect its availability to cellular regulation. Energy transfer remains its most abundant known role.
NAD+ is the oxidized electron acceptor, while NADH is the reduced electron carrier. They form a reversible redox pair and differ by a hydride ion. Cells maintain different ratios of the two depending on conditions and compartment.
NAD+ is an oxidized dinucleotide coenzyme that carries electrons in metabolic reactions. It is also consumed by signaling enzymes, including sirtuins and PARPs. Its reduced form is NADH.