before we begin…….. which of the b vitamins is the other name for niacin? a) b1 b) b3 c) b5 d)...
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Before we begin…….
Which of the B vitamins is the other name for Niacin?
a) B1b) B3c) B5d) B7
Which of the B vitamins is the other name for Niacin?
a) B1b) B3c) B5d) B7
Which amino acid can Niacin be synthesized from?
a) Prolineb) Alaninec) Tryptophand) Tyrosine
Which amino acid can Niacin be synthesized from?
a) Prolineb) Alaninec) Tryptophand) Tyrosine
Niacin deficiency can lead to:a) Anemiab) Seizuresc) Scurvyd) Pellagra
Niacin deficiency can lead to:a) Anemiab) Seizuresc) Scurvyd) Pellagra
Niacin
Kirsten Boestfleisch, Lindsay Edmonds,Lena Husnay, Sarah Johnson
NiacinVitamin B3 or nicotinic acidInositol hexaniacinate is also another
formDirectly converted to nicotinamideNiacin, nicotinic acid, and
nicotinamide are cofactors for:NAD+
NADP+
*Both are involved in energy productionWater soluble (body does not store it)Highest concentrations are found in
the liver as NAD+
Niacincommons.wikimedia.org
Nicotinamide
Food SourcesPlant products
Wheat branCornEnriched breads and cerealsLegumesNuts
Meat products – NAD+ and NADP coenzymesReleased during cooking
Need fortification
Why is Niacin Necessary?Necessary for the metabolism of
carbohydrates into glucose, which is used for energy
Helps the body use fat and proteinBoost immune system to fight disease Healthy liverProper function of the nervous systemImproves circulation
Synthesis from TryptophanNicotinamide can be synthesized from
tryptophanInefficient process: 1 mg of niacin needs 60
mg of tryptophanNiacin deficiency oftentimes results when
both niacin and tryptophan levels are insufficient
Major Functions1. Energy metabolism – NAD+ is reduced to NADH in several reactions:
Glycolytic reactionsOxidative decarboxylation of pyruvateOxidation of acetate in the TCA cycleOxidation of alcoholBeta oxidation of fatty acids Many other cellular oxidation reactions
Oxidation of NADH allows transfer of electrons in the electron transport chain to produce ATP.
Major Functions Continued2. NADP+ is reduced to NADPH
Pentose phosphate pathway Malate-pyruvate shuttle (crosses
mitochondrial membrane)
NADPH becomes a reducing agent for many cellular macromolecules, manufacture of
deoxyribonucleotides, cholesterol synthesis, and fatty acid production.
Major Functions Continued3. Poly(ADP-ribosyl)ation reactions
DNA metabolism and genomic stability
4. Mono(ADP-ribosyl)ation reactionsADP-ribose attaches to amino acid side
chains to make mono(ADP-ribose)Aids cyclic ADP-ribose and NAADP formationAllows control of intracellular calcium levels
= cellular signaling
Major Functions Continued*Cyclic ADP-ribose
Synthesis: ADP-ribose attaches to an internal ribose linkage
Important regulator of the CICR (calcium-induced calcium release)
Other regulators of calcium release:Inositol-1,4,5-triphosphate (IP3) - a type of
calcium channel NAADP (a contaminate of NADP found to
mobilize calcium)
Major Functions continued5. SIR2 (rats)/SIRT1 (humans) deacetylation reactions
Involved in genomic stability and expression particularly through:
Histones – involved in DNA transcriptionProtein p53 – tumor suppressor
A deficiency in niacin could result in a more active gene expression in DNA, making DNA
more susceptible to structural damage.
Specific AbsorptionSome in stomach liningMostly in small intestineAt low concentrations:
Sodium-dependent facilitated diffusionCarrier-mediated transportAnion antiporters
Transport MechanismPortal circulation
Facilitated diffusion into erythrocytes Nicotinic acid or nicotinamide
Liver Formation of NAD from tryptophan,
nicotinamide, or nicotinic acid Products for urinary excretion
Mechanism of Action on Various Tissues
1 & 2: Niacin Action in the Adipose TissueAffects: adipocyteTargets: HCAR2 receptor Leads to:
Decreased lipolysisDecreased VLDL and triglycerides
3 & 4: Niacin Action in the ArteryAffects: endotheliumTargets:
NAD+ phosphate Lowers LDL oxidation –
Decreases vascular inflammationRedox sensitive genes
Lowers MCP-1 and VCAM-1 – Decreases vascular inflammation
5-7: Niacin Action in the LiverAffects: hepatocyteTargets:
Enzyme/receptor DGAT2 Decreases triglyceride synthesis and Apo B
secretion – Lowers VLDL and triglycerides, Apo B, and increases LDL particle size
Beta-chain ATP synthase Lowers HDL catabolism –
Increases lipoprotein A-1 and HDL2
ToxicityShort-term:
VasodilationFlushing Burning in the face
and handsNausea and vomiting
*High dose is considered over 100mg per day
Long-term:HyperpigmentationAbnormal glucose
toleranceHyperuricemiaPeptic ulcersHepatomegalyJaundice
DeficiencySymptoms of mild deficiency: indigestion,
fatigue, canker sores, vomiting, depressionPellagra is associated with severe deficiency
Characterized by the four D’s:DiarrheaDementia Sun-sensitive dermatitis Even death
Associated with AIDS, alcohol abuse, anorexia nervosa, cancer patients
Pellagra Continued“Casals Necklace”Widespread in Europe in the 18th centuryHigh incidence in SE states of the US
During the early 20th century associated with new imports of corn from
EuropeAny guesses why?
Led to fortification of nicotinic acid and tryptophan in many foods
www.odermatol.com
Forms of Niacin as SupplementsNiacin used to treat:
Hartnup’s disease, poor glucose tolerance, IDDM, atherosclerosis, schizophrenia, hyperlipidemia, skin disorders
*Lipid soluble derivative of nicotinic acid for hyperlipidemia
Niacinamide used for:Chemotherapy and also IDDM
Tablet or capsuleRegular or extended-released (fewer side effects but
increased risk of liver damage)*When supplementing with niacin, it is recommended
that liver function tests be performed periodically
Clinical InteractionsAntibiotics (tetracycline)AspirinAnti-seizure medicationAnti-coagulants (blood thinners)Blood pressure medications (Alpha-blockers)Cholesterol-lowering medicationsStatinsDiabetes medicationsIsoniazid (INH)Nicotine patches
Take AwayNiacin supplies NAD+ to be reduced to NADHDeficiencies lead to PellagraNiacin can improve cardiovascular health by
increasing HDL and lowering LDL
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