Niacin (Vitamin B3)

Sources of niacin equivalents

I.  Chemistry

  1. Structure
  2. Coenzymes containing nicotinamide
  3. Oxidation and reduction of nicotinamide moiety

II.  Sources of niacin equivalents

  1. NAD may be synthesized from Tryptophan in the liver
    1. 1g complete, high-quality protein contains 10 mg tryptophan
    2. 60 mg tryptophan generates 1 mg niacin equivalents
    3. Therefore, 6 g protein = 60 mg tryptophan = 1 mg niacin equivalents
  2. B.  Dietary sources
    1. Milk (tryptophan)
    2. Fish, beef, chicken, turkey, port, other meats
    3. NAD and NADP undergo hydrolysis following slaughter so meats provide free nicotinamide
  3. C.  Cereal grains, seeds, and legumes (except corn)
    1. Niacin in corn is bound and unavailable
      1. Nound niacin for be released by alkali
      2. American Indians soaked corn in lime or potash solutions in making hominy and before grinding meal
    2. Jowar, a millet used in India, is also pellagragenic
      1. Unlike corn, its nicotinic acid is free
      2. It has a good tryptophan content
      3. Like corn, it is relatively high in leucine
      4. Excess leucine inhibits a key enzyme (quinolinate phosphoribosyltransferase) in conversion of tryptophan to NAD
      5. Leucine also stimulates a key enzyme (picolinate carboxylase) in the degradation pathway of tryptophan
  4. D. Tea and Coffee
    1. Trigonellin in raw-coffee is converted to nicotinic acid on roasting
    2. Absence of pellagra in Central and South American countries whose staple is corn is attributed to widespread consumption of coffee

III.  Functions

  1. Approximately 200 enzymes, primarily dehydrogenases, require NAD and NADP
  2. Functions of NAD and NADP in the cells are quite different
    1. The major role of NADH is to transfer electrons from intermediated through the electron transport chain to produce ATP
    2. Oxidative reactions in which NAD is reduced to NADH. Examples are:
      1. Glycolysis - glucose is degraded into pyruvate
      2. Oxidative decarboxylation of pyruvate
      3. Oxidation of acetate via the tricarboxylic acid cycle
      4. B-Oxidation of fatty acids
      5. NAD is required for catabolism of vitamin B6 (pyridoxal) to its excretory product (pyridoxic acid)
    3. NAD has some nonredox functions
      1. NAD acts as a donor of ADP ribose for posttranslational modification of proteins. This suggests niacin is involved in growth and differentiation of cells
      2. Niacin along with chromium is thought to be a component of glucose tolerance factor (GTF)
    4. Functions of NADP
      1. Hexose monophosphate shunt which generates important intermediates not produced in other pathways (pentose phosphates, NADPH)
      2. Malate shuttle which transports acetyl CoA out of the mitochondria
    5. NADPH is used in a variety of reductive biosyntheses
      1. Fatty acid synthesis
      2. Cholesterol and steroid hormone synthesis
      3. Oxidation of glutamate
      4. Synthesis of deoxyribonucleotides
      5. Reduction of vitamin C
      6. Glutamine reductase (GSSG ® 2GSH) requires NADPH
      7. Conversion of folate to its active forms

IV.  Metabolism

  1. Absorption and Transport
    1. NAD and NADP are hydrolyzed in the intestinal tract to release nicotinamide
    2. Nicotinamide and nicotinic acid are absorbed primarily from the small intestine
      1. By a Na-dependent, saturable system at low concentrations
      2. By passive diffusion at high concentrations
    3. Nicotinic acid converted into nicotinamide in the mucosal cells
      1. First incorporated into NAD
      2. Then released through NAD hydrolysis
    4. Found in plasma primarily as nicotinamide
    5. Nicotinamide and nicotinic acid cross cell membranes by simple diffusion (kidney tubules and red blood cells require a Na-dependent carrier system)
    6. Nicotinamide is taken up by the tissues and incorporated into the coenzymes
  2. B.  Excretion
    1. NAD and NADP can be degraded by glycohydrolase into nicotinamide and ADP-ribose
    2. Nicotinamide is methylated and oxidized into a variety of products excreted in urine

V.  Requirements

  1. Estimation of niacin requirements is complicated by tryptophan-derived NAD which is affected by a variety of influences
    1. Amount of tryptophan and niacin ingested
    2. Protein and energy intake
    3. Adequacy of riboflavin and vitamin B6
  2. Recommendations in humans are given in niacin equivalents (NE)
    1. Adult human.........9.2-13.3 NE
    2. Swine...................5-10 mg/lb feed
    3. Chicks..................12 mg/lb feed
    4. Dogs....................100-180 mg/lb BW/day

VI.  Deficiency

  1. Human – Pellagra
    1. Dermatitis of areas subject to mechanical urolutein, photosensitivity
    2. Dementia (May be due to elevated pyruvate)
      1. Irritability
      2. Headaches
      3. Sleeplessness
      4. Loss of memory
      5. Delirium
    3. Diarrhea, indigestion and anorexia
    4. Glossitis - scarlet red tongue
  2. Dog – Black tongue
    1. Inflammation of gums, redness of palate
    2. Beet red tongue with black necrotic areas
    3. Bloody diarrhea
  3. Chick
    1. Inflammation of mouth, esophagus and crop
    2. Poor feathering
    3. Normocytic anemia
  4. Pigs
    1. Diarrhea, vomiting
    2. Dermatitis
    3. Normocytic anemia

VII.  Toxicity

  1. Niacin is not stored and appears to be relatively nontoxic in large doses
  2. 3-6 g/day is sometimes used to lower serum cholesterol and low density lipoproteins but may have side effects
    1. Release of histamine resulting in uncomfortable flushing
    2. Possible liver damage
    3. Competition of niacin with uric acid thereby increasing serum urate
    4. Dermatologic problems, itching
    5. Elevated plasma glucose

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