2HistoryThe term niacin (vitamin B3) is considered a generic term for nicotinic acid and nicotinamide (also called niacinamide).The vitamin was once called the anti–black tongue factor because of its effect in dogs.Pellagra was especially prevalent in the Southern United States where corn (which contains a relatively unavailable form of niacin) was a main dietary staple in the early 1900s.In 1937 Elvehjem isolated the vitamin, which was shown then to cure both pellagra and black tongue.
3Niacin (nicotinamide) Vitamin B3 The vitamin activity of niacin is provided by both nicotinic acid and nicotinamide.Structurally, nicotinic acid is pyridine 3-carboxylic acid, whereas nicotinamide is nicotinic acid amide.
4SourcesThe best sources of niacin include: fish such as tuna and halibut, and meats such as beef, chicken, turkey, among others. Enriched cereals and bread products, whole grains, fortified cereals, seeds, and legumes.Contain appreciable amounts of niacin in coffee and tea.lesser amounts in green vegetables and milk.In supplements, niacin is generally found as nicotinamide (niacinamide).
5SourcesIn animals, niacin occurs mainly as nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).But, after slighting of animals, NAD and NADP are thought to undergo hydrolysis; thus, meats provide niacin as free nicotinamide.In their oxidized forms, NAD and NADP possess a positive charge and therefore may alternatively be written NAD+ and NADP+.
8DIGESTION, ABSORPTION, TRANSPORT, AND STORAGE NAD and NADP may be hydrolyzed within the intestinal tract or enterocyte by glycohydrolase to release free nicotinamide.GlycohydrolaseNAD & NADP NicotinamideNicotinamide and nicotinic acid can be absorbed in thestomach, but they are more readily absorbed in the smallintestine
9DIGESTION, ABSORPTION, TRANSPORT, AND STORAGE In the small intestine, if niacin concentrations is low, its absorbed by sodium-dependent, carrier-mediated (facilitated) diffusion.At high concentrations (as with 3–4 g pharmacological doses), niacin is absorbed almost completely by passive diffusion.In the plasma, niacin is found primarily as nicotinamide, with little nicotinic acid. Up to ~1/3 of plasma nicotinic acid is bound to proteins.Nicotinamide and nicotinic acid move across cell membranes by simple diffusion.Then, nicotinic acid transport into the kidney tubules and red blood cells requires a carrier.
10DIGESTION, ABSORPTION, TRANSPORT, AND STORAGE Nicotinamide is primary precursor of NAD in all tissues.Nicotinic acid may be used to synthesize NAD in the liver which influenced by various hormones.Vitamin is trapped within the cell as NAD or NADP.Intracellular concentrations of NAD typically predominate over those of NADP.
11DIGESTION, ABSORPTION, TRANSPORT, AND STORAGE In the liver, excess niacin and tryptophan are converted to NAD and stored in small amounts not bound to enzymes.NAD may be degraded to yield nicotinamide, which then is available for transport to other tissues.NAD is found primarily in its oxidized form (NAD+), whereas NADP is found in cells mainly in its reduced form (NADPH).
12FUNCTIONS AND MECHANISMS OF ACTION Approximately 200 enzymes, primarily dehydrogenases, require the coenzymes NAD and NADP, which act as a hydrogen donor or electron acceptor.Niacin functions as a substrate in nonredox roles as a donor of adenosine diphosphate ribose (ADP-ribose).
13FUNCTIONS AND MECHANISMS OF ACTION CoenzymesNAD and NADP are very similar and undergo reversible reduction in the same way, their functions in the cell are quite different.The major role of NADH is to transfer its electrons from metabolic intermediates through the electron transport chain thereby producing adenosine triphosphate (ATP).NADPH: acts as a reducing agent in many biosynthetic pathways such as (fatty acid, cholesterol, and steroid hormone synthesis).
14FUNCTIONS AND MECHANISMS OF ACTION CoenzymesNAD and NADP are tightly bound to their apoenzymes and can easily transport hydrogen atoms from one part of the cell to another.These reactions occur in the mitochondria and in the cytoplasm.
15FUNCTIONS AND MECHANISMS OF ACTION CoenzymesOxidative reactions in which NAD participates and is reduced to NADH include:Glycolysisoxidative decarboxylation of pyruvateoxidation of acetyl CoA in the TCA cycleβ-oxidation of fatty acidsoxidation of ethanolNAD is required for catabolism of vitamin B6 as pyridoxal to its excretory product, pyridoxic acid.
16FUNCTIONS AND MECHANISMS OF ACTION CoenzymesNADPH is generated from NADP by reduction which occurs as part of the hexose monophosphate shunt by the mitochondrial.The NADPH producedin is used in some reductive biosynthesis:fatty acid synthesischolesterol and steroid hormone synthesisoxidation of glutamatesynthesis of deoxyribonucleotides (precursors of DNA)regeneration of glutathione, vitamin C, and thioredoxinconversion of folate to active forms, dihydrofolate (DHF) and tetrahydrofolate (THF) and synthesis of 5-methyl THF and 5,10-methylene THF.
17METABOLISM AND EXCRETION NAD, generated from nicotinamide or produced in the liver from tryptophan, and NADP can be degraded by glycohydrolase into nicotinamide and ADP-ribose.The released nicotinamide is methylated and is then oxidized in the liver into a variety of products that are excreted in the urine.Typically, little nicotinic acid or nicotinamide is excreted, because both compounds may be actively reabsorbed from glomerular filtrate.
18METABOLISM AND EXCRETION The primary metabolites of nicotinamide are:N' methyl nicotinamide (~20% to 30% of niacin metabolites).N' methyl 2-pyridone 5-carboxamide (~40% to 60%).N' methyl 4-pyridone carboxamide (4-pyridone) in small amounts.Nicotinic acid is metabolized mainly to N‘ methylnicotinic acid.
19RDA’sRecommendations for niacin intake include calculations of niacin derived from the amino acid tryptophan (about 60 mg of tryptophan thought to generate 1 mg of niacin).Total niacin thus is provided to the body as nicotinic acid and nicotinamide and from 1/60 mg of tryptophan.The term niacin equivalent (NE) is used to account for the provision by tryptophan.Assuming that:1 g of high- quality protein in diet = 10 mg of tryptophan.Intake 60 g complete protein = 600mg tryptophan.60mg tryptophan /1mg of NE60g protein = 10 NEs
20RDA’s The RDA’s for niacin (as niacin equivalents) 14 mg/day for women 16 mg/day for men18 mg/day for pregnancy17 mg/day for lactation
21DEFICIENCY: PELLAGRA Pellagra is a serious deficiency of niacin. Pellagra can easily remembered as the four Ds—dermatitis, dementia, diarrhea, and death—are often used as a mnemonic device for remembering.The dermatitis sunburn in face and neck then in hands, wrists, elbows, knees, and feet.Neurological: headache, loss of memory, peripheral neuritis and dementia or delirium.Gastrointestinal: glossitis, stomatitis, nausea, vomiting, and diarrhea or constipation.If untreated, death occurs.
23TOXICITYLarge doses of nicotinic acid (up to 6 g/day in divided doses) are used to treat hypercholesterolemia (high blood cholesterol).These pharmacological doses:significantly lower total serum cholesterol, triglycerides, and low-density lipoproteins (LDLs) and increase high-density lipoproteins (HDLs).Inhibits lipolysis in adipose tissue and decreases hepatic VLDL secretion from the liver and LDL production.Diminish triglyceride synthesis and increases HDL in liver.
24TOXICITYThese dose of vitamin has some undesirable side effects, especially in doses of 1 g or more per day.Vasodilatory effects: including uncomfortable flushing and redness alongnwith burning, itching (pruritus), tingling, and headachesgastrointestinal problems such as heartburn, nausea, and possibly vomiting.liver injury (hepatic toxicity) elevated hepatic enzymes, jaundice, hepatitis and liver failure.Hyperuricemia (raising serum uric acid levels).Elevation of plasma glucose concentrations (i.e., glucoseintolerance).