AKA:

*B3

*Nicotinic acid

*Nicotinamide

Structures of NAD+ and NADP+

*Fish (Tuna & Halibut), meat (beef, poultry, pork)

*Enriched cereals, bread products, whole grains, seeds, legumes

*Coffee & Tea

*In supplements as nicotinamide

*In some foods, niacin may be covalently bound to niacytin (complex carbs) or niacinogens (small peptides)

*Not readily absorbed

-Only 10% of the niacin from corn absorbed

-Lime treatments can improve availability of bound niacin

*Tryptophan to NAD+ to NADP+

*In Liver

*In SI

*Na⁺- dep active transport at low concentration

-Passive diffusion at high concentration

*In plasma, niacin found as nicotinamide and some nicotinic acid

-Up to 1/3 of nicotinic acid is bound to plasma proteins

*From blood, nicotinamide and nicotinic acid move across cell membranes by diffusion

-Transport into kidney tubules and RBCs requires a carrier

*Inside cells, nicotinamide is converted to NAD⁺ and phosphorylated to make NADP⁺

*Niacin, as NAD⁺/NADH or NADP⁺/NADPH is trapped in the cell

*Intracellular [NAD] > [NADP]

*In liver, excess niacin and Trp are converted to and stored as NAD⁺ (small amounts)

*NAD⁺ can can be degraded to nicotinamide and released to blood for other tissues

*NAD is found primarily in oxidized form (NAD⁺), whereas NADP is found in reduced form (NADPH)

*There is little loss of niacin in urine when intake is average. (Both vitamers are actively reabsorbed in kidney)

*NAD (from nicotinamide or Trp) and NADP can be degraded to nicotinamide

*Excess nicotinamide and nicotinic acid are methylated and further oxidized in liver into urinary metabolites

*Coenzymatic Role

-NAD and NADP for metabolic intermediates

-TCA

-ETC

*Non-coenzymatic role

-As a substrate: donor of ADP-ribose

-Post-translational modification of protein

-Cell regulation

*NAD⁺/NADH: e- transfer: ATP production through ETC

*NADP⁺/NADPH: acts as a reducing agent in FA, cholesterol, hormone synthesis and in other pathways

*NAD and NADP coenzymes are tightly bound to their apoenzymes and can transport H atoms in the mito and in cytoplasm

NAD+/NADH in the TCA cycle

*NAD/NADH: e- transfer

-Glycolysis

-Oxidative decarboxylation of pyruvate

-Oxidation of acetyl CoA in TCA 

-Beta Ox of FA

-Ox of ethanol (NADP/NADPH)

*The NADPH produced in these rxns is used in reductive biosynthesis

-FA synthesis

-Cholesterol and steroid hormones synthesis

-Oxidation of glutamate by glutamate DH (glu->alphaKG)

-Synthesis of DNA

-Regeneration of GSH from GSSG, AA from DHA, and thioredoxin (SS->SH)

NAD+/NADH: Oxidation of acetyl CoA in the TCA cycle

NAD+/NADH: Oxidation

*The e- derived are transferred to ETC through oxidation of NADH

*The energy resulting from these transfers generates ATP (2.5ATP/NADH)

NADP+/NADPH: Oxidation

Pentose Phosphate Pathway

Glutathione and NADPH

Folate and NADPH

NADPH and Nitric Oxide

*NADPH needed for nitric oxide synthesis

*L-arginine + NADPH + H+ + O2 = citrulline + NO + NADP+

-increased blood flow

-too much = toxic

*NAD as a substrate of ADP-ribose for the posttranslational modification of proteins

*In mammals, ADP-ribosylated proteins function

-DNA repair

-DNA replication

-Cell differentiation

*"Niacin Equivalents" is used since we get niacin from tryptophan

*RDA Men: 16mg NE/d

*RDA Women: 14mg NE/d

*60 mg of Tryptophan = 1mg of niacin = 1 niacin equivalent

*4-5 hrs after given 50mg of Niacin, [urinary metabolites] are measured

*<0.8mg/d of N' methyl nicotinamide (NMN) = deficiency

*<0.5mg NMN/g creatine = deficiency

*>1.6mg NMN/g creatinine = adequate

*Pellagra ("rough skin")

*Affects skin, dig tract, brain

*People who live in areas where maize is the main food source are at risk of developing pellagra bc the niacin in it can't be absorbed in the intestine unless the maize is treated with alkali as it is w/tortillas

-Treatable with oral dose of niacin

*Pellagra

*Alcoholics and undernourished people are at risk

*Inadequate intake of iron, riboflavin, and vit B6 increases the risk of niacin deficiency

*People who have Hartnup disease can develop pellagra bc decreases intestinal transport and renal resorption of tryptophan

*Pellagra Symptoms

*4 D's: Dermatitis, Dementia, Diarrhea, Death

*Symmetric, dark red rash on hands, feet, calves, around neck, face

*Skin abnormalities are persistent and affected areas may become brown and scaly

*Pellagra Symptoms

*Whole dig tract is affected including nausea, vomiting, abdominal discomfort, constipation, diarrhea

*Later:  fatigue, insomnia, apathy

*Malfunction of brain usually follows: confusion, disorientation, hallucinations, memory loss

*High ROS = High lipid peroxidation, DNA damage and depletion of NAD⁺ = disordered cellular metabolism

*NAD⁺ plays essential roles in ATP production and secondary messenger signaling, transcriptional regulation and DNA repair

*Maintaining intracellular NAD⁺ pools may prove the protection of this age-dependent cellular damage

*UL: 35mg/d 

*High doses of nicotinic acid are used to lower high cholesterol, triglyceride, and LDL levels

*Adverse effects: red flushing, itchy skin, liver damage, increase blood glucose levels

*Niacin

*Blocks release of triglycerides from adipose and synthesis in liver

*Lowers total cholesterol, LDL, VLDL, and raises HDL

*1000-2000mg 1-3x per day

*Also effective when added to statins