1. NUTR 624 – Vitamin Metabolism 6/25/2014 Chantal Otelsberg
Niacin (Vitamin B3)
NUTR 624 – Vitamin Metabolism
6/25/2014
Chantal Otelsberg

2. Niacin (B3)
In terms of dietary intake, the combination of nicotinic acid and nucleotide-bound nicotinamide=niacin status
Tryptophan is the third form of B3 that that is a precursor to for NAD (essential amino acid)
Nicotinomide is the form of Niacin in supplements

3. Where do I find Niacin?

4. Historical Anecdotes Based on niacin deficiency, corn contains niacin
Corn is a tightly bound structure, which is heat stable and is sensitive to alkaline treatment
Native Americans developed various alkaline processing techniques to release existing niacin
Importance of process not recognized when Columbus brought corn to Europe
Pellagra outbreak occurred in outdoor labor workers, where sun-induced lesions occurred among those niacin deficient
Similar outbreaks in Spain, Italy, and Egypt during 1700s and 1800s
Nicotonic Acid first isolated in 1867, active role of vitamin was not identified until 1937
1906-NAD+ identified in yeast extracts
Redox capabilities understood in 1936
1915-Dr. Joseph Goldberger:
Conducted clinical trials on pellagra induced prison populations
Pellagra cured/prevented through balanced diet and yeast supplements
1949-NADH formation with ATP production understood
1966-first publication on ATP-ribose formation, which aided in understanding pellagra

5. Digestion of Niacin
NAD and NADP needed to enable absorption, both present in food
B6(pyrophosphatase) required for phosphate hydrolysis of NADP
Due to negative electron charge of phosphate
Nicotinomide and nicotinic acid absorbed in stomach
More readily absorbed in the small intestine (sodium dependent facilitated diffusion)
High concentration of Niacin, passive diffusion

6. Absorption
Nicotinamide and nicotinic acid formed slowly in stomach lining
Absorption in small intestine more rapid
Mechanisms of absorption not clear in current research
Nucleotides degraded in upper small intestine to form free nicotinamide
Low concentrations absorbed by sodium- dependent faciliated diffusion/proton cotransportors/anion antiporters
Higher concentrations absorbed by passive diffusion

7. Absorption Absorbed through brush border in small intestine
Nicotinamide converted to NADportal circulation Liver takes up remaining nicotinic acid from portal blood
Nicotinic Acid and Tryptophan converted to NAD once in the liver

8. Transport
In plasma-niacin found in nicotinic amide bloodand nicotinic acid
1/3 of nicotinic acid (plasma) bound to plasma proteins
bloodnicotinamide and acidcell membrane by simple diffusion
Nicotinic acid transport kidney tubules and red blood cells require carrier

9. Metabolic Function Coenzyme Non-redox Roles
Transfer H electrons from one part of cell to another
Provide energy to fuel metabolic reactions
Aiding electron transport chain
NAD acts as donor to form ADP-ribose and of modification of proteins associated with chromosomes
Needed for DNA repair, replication, and transcription

10. Niacin Deficiency
Originally thought to be caused by disruptions in redox cycling (only metabolic role of niacin at the time)
Due to ADP-ribosylation functions of NAD
Deficiency mainly caused by NAD+ pool depletion
Malabsorption
Increased sensitivity to DNA damage
Cancer
Bone Marrow
Esophagitis and Esophogeal ulcerations

11. Deficiency Four D’s of deficiency: Dermatitis Dementia/Delerium
Pellagra – “rough skin”
Similar to sunburn
Dementia/Delerium
Headache/apathy
Loss of memory
confusion
Diarrhea
Gastrointestinal manifestations
Death
If left untreated

12. Treatment 500 mg of nicotinamide daily –several weeks
Possible riboflavin supplementation to oral lesions
Possible thiamin supplementation for treatment of peripheral nerve problems

13. DRI/RDI/AI Infants 0 - 6 months: 2* milligrams per day (mg/day)
months: 4* mg/day
*Adequate Intake (AI)
Children
1 - 3 years: 6 mg/day
4 - 8 years: 8 mg/day
years: 12 mg/day
Adolescents and Adults
Males age 14 and older: 16 mg/day
Females age 14 and older: 14 mg/day
Tolerable Upper Limit
Children – mg/d
Adults – 35 mg/d
*vasodilatory effects

14. Assessment Urinary metabolites through urinalysis
Serum and red blood cell indicators due to NAD concentrations related to NAD:NADP concentration in erythrocytes

15. Interactions Niacin synthesized in body from tryptophan
Scientists are currently debating how important the tryptophan to niacin pathway is in human nutrition
Process requires vitamin B6 to occur
Therefore, tryptophan and vitamin B6 could increase deficiency of niacin

16. Primary Research
Majewski, M., & Lebiedzinska, A. (2014). The evaluation of selected shellfish as a source of niacin in nutrition and therapy of modern human. Polish Annals of Medicine, 69.
Niacin analysis that was conducted showed differences between the various types of seafood
Microbial method
Vitamin extracted using enzymatic hydrolysis – papain and diastase
Used 100g of seafood for DRI for men and women
Among the analyzed seafood, the best source of niacin came from the 100 g of oyster meat (containing 1.16 mg niacin)
Determined that increased consumption of seafood might contribute to reduce the risk of civilization diseases morbidity,

17. Critical Thinking
Diagram/Describe the several general areas of metabolism in which NAD(NADH) and NADP(H)-dependent enzymes are involved.
Glycolysis: NAD aids the transport of hydrogen ions to pyruvate, reducing pyruvate to lactate, reaction occurs in anaerobic conditions and lactic acid build up occurs during physical activity, also functions in aerobic conditions
Oxidative decarboxylation of pyruvate to acetyl-CoA in TCA cycle: same process as glycolysis, NAD + oxidizes FADH2 and taking hydrogens-becoming NADH
Oxidative of acetyl-CoA in TCA: reoxidation of NADH to produce ATP through oxidative phosphorylation
Beta Oxidation of Fatty Acids: same oxidation process as oxidation of acetyl CoA, creating energy
Oxidation of ethanol: an accumulation of NADH increases during the oxidation of ethanol, slows process of TCA cycle
NADP/NADH
Fatty acid synthesis: NADPH serves as hydrogen donor in the formation of fatty acid synthesis
Cholesterol and Steroid Hormone synthesis: \(NADPH) is a coenzyme for many of the reductive biosynthesis steps in this pathway, acting as a reducing agent
Proline synthesis: amino acid that acts as a reducing agent
DNA synthesis: same process as fatty acid synthesis, NADPH donates hydrogen to aid dihydrofolate to become tetrahydrofolate Glutatione/vitamin C/thioredoxin regeneration:
Folate conenzyme synthesis, tetrahyrdofolate, 5-methyl THF, and 5,10-methylene THF:

18. References
Majewski, M., & Lebiedzinska, A. (2014). The evaluation of selected shellfish as a source of niacin in nutrition and therapy of modern human. Polish Annals of Medicine, 69. Gropper, S. A., Smith, J. L., & Groff, J. L. (2009). Advanced nutrition and human metabolism. Australia: Wadsworth/Cengage Learning. Shils, M. E., & Shike, M. (2006). Modern nutrition in health and disease. Philadelphia: Lippincott Williams & Wilkins. Deficiency Diseases (History of Medicine). (n.d.). Retrieved from deficdis.html Guide to Vitamn B3-Niacin (Nicotinic Acid). (n.d.). Retrieved from Niacin: MedlinePlus Medical Encyclopedia. (n.d.). Retrieved from

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