1. Late 1940s, the role of deficiency of niacin in the aetiology of pellagra was realized
2. Large losses during milling process of cereals because of min amount of bran and germ which the valuable sources of niacin and other micronutrients
2.1. Strategies to increase niacin in foods
2.1.1. Germination
2.1.1.1. sprouting of cereal and legume brought about by soaking in water.
2.1.1.2. niacin increase 3 fold and 1.8 fold in sprouts and de-sprouted maize
2.1.2. Fermentation
2.1.2.1. increase in nutritive value of maize meal
2.1.2.2. West Africa - increase niacin, other vitamin as well as tryptophan and lysine in whole grain maize
2.1.2.3. Van Veen and Steinkraus - increase nearly 7 fold in the making of Indonesian tempeh e.g 0.9mg niacin/g (soybean) -> 6.0 mg niacin/g (tempeh)
2.1.3. Fortification
2.1.3.1. Codex Alimentarius 1987
2.1.3.1.1. replace losses
2.1.3.1.2. ensure nutritional equivalence
2.1.3.1.3. standardization
2.1.3.1.4. provide balance intake of micronutrients
3. Niacin and Tryptophan Deficiency
3.1. Photosensitive dermatitis, like severe burn and butterfly like pattern distribution over the face and all part of skin that is exposed to sunlight.
3.2. Advanced stages : cause dementia, depressive psychosis and diarrhoea. Untreated may lead to fatal.
3.3. Increased catabolism of the amino acid histidine lead to a reduction in the conc. of urocanic acid, histidine metabolite that is the major UV-absorbing compound in normal dermis.
3.4. Depressive psychosis may be the result of tryptophan depletion lead lower availability of tryptophan for synthesis of the neurotransmitter serotonin (5-hydroxytryptophan).
3.5. The cADP-ribose and NAADP controlling calcium release in response to neurotransmitter and impaired energy yielding metabolism in the CNS as a result of NAD(P) depletion.
3.6. Diarrhoea cause by rectal inflammation can ceased after 5-7 days starting treatment with niacin.
3.7. WHO: pellagra is due to a lack of the vitamin niacin or its precursor tryptophan. Associated with diet with non-alkali treated maize. Outbreak 1950s cause by overheating of infant milk formula.
4. Tryptophan metabolism is disturbed or intake of amino acid is inadequate -> niacin become dietary essential
5. Nicotinamide nucleotide coenzymes function as electron carriers in redox reaction
6. Nicotinic acid and nicotinamide have equal biological activity
6.1. 60mg of tryptophan = 1 mg of dietary preformed niacin
6.2. Requirement of intakes = mg of niacin equivalents- the sum of preformed niacin + 1/60 x tryptophan
7. Metabolism of Niacin
7.1. 1. Digestion and Absorption
7.1.1. Present largely in the tissues as nicotinamide nucleotides.
7.1.2. Nicotinamide nucleotides in the intestinal lumen are hydrolyzed to nicotinamide.
7.1.3. Intestinal bac deaminated nicotinamide
7.1.4. Nicotinic acid and nicotinamide are absorbed from the small intestine by sodium-dependent saturable process
7.2. 2. Unavailable Niacin in Cereals
7.2.1. Niacin in the cereals is biologically unavailable - bound by niacytin-nicotinoyl esters.
7.2.2. Small fraction may be available in niacytin as a result from hydrolysis by gastric acid.
7.2.3. 10% release as free nicotinic acid after extraction of maize or sorghum meal with 0.1 mol per L HCL
7.2.4. Treatment of cereals with alkali (soaking) and baking alkali with baking powder releases much of nicotinic acid result in lower pellagra prevalence in Mexico.
7.3. 3. Synthesis of the Nicotinamide Nucleotide Coenzymes
7.3.1. The nicotinamide nucleotide coenzymes NAD and NADP can be synthesis from niacin vitamers or quinolinic acid
7.3.2. DIRECT - NA catalyzed by phosphoribosyltranferase -> NAMN -> NAAD by the action of nicotinic acid mononucleotide pyrophosphorylase -> NAD
7.3.3. INDIRECT - deamination to nicotinic acid catalyzed by nicotinamide deamidase.
7.3.4. Dicarboxylic acid intermediate in the quinolinate phosphoribosyltranferase reaction undergoes spontaneous decarboxylation to nicotinic acid mononucleotide.
7.3.5. Major roles of liver - synthesize NAD(P) from tryptophan followed by hydrolysis to release niacin for use by extrahepatic tissues.
7.4. 4. Catabolism of NAD(P)
7.4.1. Catabolized by 4 enzymes that act on oxidized but not reduced coenzymes
7.4.1.1. NAD pyrophosphatase
7.4.1.1.1. release nicotinamide mononucleotide
7.4.1.1.2. hydrolyzed by NAD glycohydrolase to release nicotinamide
7.4.1.1.3. substrate for nicotinamide mononucleotide pyrophosphorylase to form NAD
7.4.1.2. NAD glycohydrolase
7.4.1.2.1. releases nicotinamide and ADP-ribose
7.4.1.2.2. catalyze the synthesis of cADP-ribose and nicotinic acid ADP (roles in intracellular signaling)
7.4.1.3. ADP-ribosyltranferase
7.4.1.3.1. catalyze ADP-ribosylation of proteins releasing nicotinamide
7.4.1.4. Poly(ADP-ribose) polymerase
7.4.1.4.1. catalyze poly-ADP ribosylation of proteins, releasing nicotinamide again
7.5. 5. Urinary Excretion of Niacin Metabolites
7.5.1. Normal conditions- no or little excretion (reabsorbed from glomerular filtrate).
7.5.2. Nicotinamide undergo oxidation to nicotinamide n-oxide.
7.5.3. Minor in humans unless large amounts is ingested but major excretory product of niacin metabolism in mouse.
7.6. 6. Synthesis of Nicotinamide Nucleotides from Tryptophan
7.6.1. 60mg of tryptophan = 1 mg of preformed niacin.
7.6.2. NAD(P) can be synthesized from tryptophan metabolite quinolinic acid.
7.6.3. Niacin equivalent and intake = niacin equivalent - sum of preformed niacin and 1/60 of tryptophan.
7.6.4. Changes in hormonal status result in changes to the ratio such as the range between 7 to 30 mg of dietary tryptophan = 1 mg of preformed niacin in late pregnancy.
7.6.5. Intakes of tryptophan also effect the ratio. Low intakes : 1 mg of tryptophan = 1/125 mg of preformed niacin.
7.7. 7. Redox Function of NAD(P)
7.7.1. Induction of indoleamine dioxygenase as a factor of tryptophan depletion that leads to pellagra.
7.7.2. NAD+ involve as an electron acceptor in energy-yielding metabolism produces NADH which then oxidized by the mitochondrial electron transport chain.
7.7.3. Major coenzyme for reductive synthetic reactions is NADPH.