Niacin, nicotinic acid, nicotinamide -- Nicotinamide adenine dinucleotide (NAD); nicotinamide adenine dinucleotide phosphate (NADP)
Adequate Intake ?:
Electron (hydrogen) transfer reactions for nutrient metabolism and energy production; ADP ribose transfer. Pellagra -- Diarrhea, dermatitis, mental confusion. Major Food Sources: Fish, meats, peanut butter. RDA: 16 mg.
Highest in animal source products and not typically a nutrient of concern.
Helps convert food into usable energy
Co-factor >500 reactions
Assists with DNA replication and repair
Tryptophan can convert to niacin at 60:1
Supplemental niacin has an Upper Tolerable level of 35 mg/day due to "flushing"
History & Discovery:
Niacin was discovered through its deficiency disease called Pellagra - described first in Italy in 1778.
Symptoms include four-D's: dermatitis, diarrhea, dementia, and ultimately death.
Pellagra reached endemic proportions in Southeast USA (3 million victims) where corn was a dietary staple.
Native Americans learned how to process corn to expose niacin. Nixtamalization process: Wash maize, Add Lime and cook, steep, drain and rinse.
Maize kernals are high in niacin and tryptophan, but locked up in the germ. Soaking kernals in alkaline solution overnight (lime or ash; pH of 10.8) followed by cooking makes these compounds bioavailable by "leaching them out" of the germ.
Tryptophan can be converted to Niacin at a 60:1 conversion ratio
Dr. Joseph Goldberger, an American-Hungarian infectious disease specialist in 1914 ran a study with 12 prisoners provided a corn-based diet of whole corn, grits, and cornbread. 6 months later, many developed pellagra. Meat was added to the corn diet and within a few weeks they were cured. Upon claims of fraud that pellagra was based on infection, Goldberger injected himself and friends with pellagra blood to show it wasn't infectious based. In the late 1910's, the Public Health Service started a campaign in the South to recommend consumption of fresh meats, milk, and eggs. Pellagra was eventually eradicated with enrichment of wheat and corn flour with niacin, thiamine, and iron.
In 1937, Conrad Elvehjem identified two vitamins, nicotinic acid (niacin) and nicotinamide--two major forms of Vitamin B3.
Animal Sourced foods are the richest source of niacin.
Animal Products: Present as nicotinamide (niacin) and its coenzyme forms: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)
Plant Products: Present as nicotinic acid. Can be bound to carbohydrates in which case it is called niacytin (only 30% bioavaible) - common in corn before nixmatilization.
Tryptophan can be converted to Niacin using FAD and B6 at a 60:1 conversion ratio becoming an important source of NAD.
NADP -> Pyrophosphatase -> NAD -> Glycohydrolase -> Nicotinamide from Meats
Plants provide nicotinic acid
Jejunum is the Primary Site of Absorption
Absorption and Storage:
NAD+ (Oxidized Form) <-> NADH (Reduced Form)NADPH (Reduced Form) <-> NADP (Oxidized Form)
Diet -> Nicotinic acid -> [Nicotinate phosphoribosyltransferase(NAPRT)] -> Nicotinic acid mononucleotide (NAMN) -> [Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1-3)] -> Nicotinic acid adenine dinucleotide (NAAD) -> NAD synthetase (NADS) -> NAD+
De novo biosynthesis pathway:
Diet -> Tryptophan -> [IDO, TDO] -> N-formylkin -> L-kin -> 3-HAA -> ACMS -> (AMS -> TCA cycle) OR Quinolinic acid -> NAMN
Diet -> Nicotinamide riboside (NR) -> Nicotinamide mononucleotide (NMN) -> [NMNAT1-3] -> NAD+ -> NAD-consuming enzymes (sirtuins, PARP, CD38, CD157) -> Nicotinamide (NAM) -> [Nicotinamide phosphoribosyltransferase (NAMPT)]>400 enzymatic reactions require NAD and NADPNAD (oxidized form) accepts hydrogens and electrons from metabolic intermediates and NADH (reduced form) carries these through the electron transport chain.
The Pairs NAD+/NADH and NADP+/NADPH have similar redox potentials, and many dehydrogenases can use either coenzyme.
NAD reduced to NADH in:Glycolysis (6th reaction)
Oxidative decarboxylation of pyruvate to acetyl-CoA
Oxidation of acetyl-CoA in the TCA cycle
B-oxidation of fatty acidsNADP is mostly present as NADPH (reduced form) and serves as an electron donor in fatty acid and steroid hormone systems, and to antioxidant systems such as thioredoxins and glutathione.
Thioredoxins are ubiquitous antioxidant enzymes that play important roles in many health-related cellular processes including protection from cancer and viral diseases.
FAD donates electrons from NADPH through its bound FAD to reduce disulfide bonds within the oxidized form of thioredoxin to bring it back to a reduced state.
Thioredoxin reductase (TrxR)NAD is also involved in about 50 different non-redox reactions in which adenosine diphosphate (ADP) ribose is transferred to acceptor molecules. Examples: DNA repair & replication, G-protein activity, IC calcium signaling.
The transfer of one (mono) ADP-ribose from NAD to various acceptor proteins occurs by the action of mono-ADP-ribosyltransferase and forms ADP-ribosylated proteins with the release of nicotinamide. NAD-dependent deacetylases, known as sirtuins, involves the cleavage of NAD generating O-acetyl-ADP-ribose (OAADPr) and the deacetylated substrate protein (histone). Sirtuins affect signaling pathways involved in DNA repair, cell differentiation, and cell cycle regulation. - "Anti-aging molecules".
Sirtuins only function in presence of NAD+. NMN as a supplement is overhyped. In catabolic pathways, the oxidation of macronutrients is coupled with the reduction of NAD+; NAD+ accepts electrons and becomes reduced (NADH)
In anabolic pathways, the oxidation of NADPH provides electrons. needed for the biosynthesis of macromolecules; NADPH donates electrons and becomes oxidized (NADP+)
Deficiency Diseases, Detection, Cures:
Cheilosis and/or glossitis
Pigmentation changes, erythema
Nervous system -- general effects