Niacin and NAD/NADP

On this page

Niacin: Introduction - The B3 Boss

  • Vitamin B3 (Niacin): A water-soluble vitamin, crucial for metabolism. Exists as:
    • Nicotinic acid ($C_6H_5NO_2$)
    • Nicotinamide ($C_6H_6N_2O$)
  • Dietary Sources: Widely available.
    • Animal: Meat (esp. liver, poultry), fish (tuna, salmon).
    • Plant: Fortified/enriched grains, legumes, nuts, seeds.
  • Endogenous Synthesis: Unique among B vitamins.
    • Precursor: Tryptophan (essential amino acid).
    • Cofactors: Vitamin B2 (Riboflavin) & B6 (Pyridoxine) are vital.
    • 📌 Ratio: 60 mg Tryptophan $\approx$ 1 mg Niacin.
  • Recommended Dietary Allowance (RDA):
    • Adults: 14-16 mg NE/day (NE = Niacin Equivalents).

Niacin, NAD, and NADP Chemical Structures

⭐ Niacin can be synthesized endogenously from the amino acid Tryptophan; approximately 60 mg of Tryptophan yields 1 mg of Niacin.

NAD/NADP: Synthesis & Roles - Electron Shuttles

  • Synthesis from Niacin (B3) & Tryptophan:
    • Preiss-Handler Pathway: Nicotinic Acid → NAD+.
    • Salvage Pathway: Nicotinamide → NAD+.
    • Tryptophan (de novo) also yields NAD+.
    • NAD+ $\xrightarrow{\text{NAD+ kinase, ATP}}$ NADP+.
  • Structure: Dinucleotide core.
    • NAD+: Nicotinamide, Adenine, 2 Ribose, 2 $P_i$.
    • NADP+: NAD+ with an additional $P_i$ on adenosine's 2'-ribose. Structures of Niacin, Nicotinamide, NAD, and NADP
  • Roles: Electron Shuttles (Coenzymes):
    • Carry $2e^-$ and $H^+$.
    • NAD+ (Catabolic): Oxidative reactions (glycolysis, TCA cycle).
      • $NAD^+ + 2e^- + 2H^+ \rightleftharpoons NADH + H^+$
    • NADP+ (Anabolic): Reductive biosynthesis (fatty acid, steroid synthesis), antioxidant.
      • $NADP^+ + 2e^- + 2H^+ \rightleftharpoons NADPH + H^+$
      • 📌 NADPH: Pentose Pathway, Protective, Producing.

⭐ NADP+ differs from NAD+ by an additional phosphate group on the 2'-hydroxyl of the adenosine moiety, and NADPH is a major electron donor in reductive biosynthesis and detoxification pathways.

NAD/NADP: Metabolic Functions - Niacin's Busy Day

Niacin (B3) derivatives $NAD^+$ & $NADPH$: key electron carriers in metabolism.

Feature$NAD^+$ (Oxidative Reactions)$NADPH$ (Reductive Biosynthesis & Detoxification)
Primary RoleCatabolic (energy yielding)Anabolic (biosynthetic), Antioxidant
Key Pathways/Enzymes- Glycolysis (e.g., Glyceraldehyde-3-P Dehydrogenase)
- PDH Complex: Pyruvate + $NAD^+$ + CoA $\rightarrow$ Acetyl-CoA + $NADH$ + $H^+$ + $CO_2$
- TCA Cycle (Isocitrate, $\alpha$-KG, Malate Dehydrogenases)
- $\beta$-oxidation
- Alcohol Dehydrogenase
- HMP Shunt (G6PD)
- Fatty acid synthesis
- Cholesterol synthesis
- Steroid synthesis
- Glutathione Reductase
- Cytochrome P450 monooxygenases

⭐ The ratio of $NAD^+/NADH$ is generally high, favoring oxidative reactions, while the ratio of $NADP^+/NADPH$ is generally low, favoring reductive biosynthetic reactions.

Niacin: Clinical Aspects - Too Little, Too Much

  • Pellagra (Deficiency): 📌 3 D's: Dermatitis (photosensitive, Casal's necklace), Diarrhea, Dementia. Can progress to Death (4th D). Casal's necklace rash in pellagra
    • Causes: Dietary lack (maize/sorghum), malabsorption, Hartnup disease, Carcinoid syndrome, Isoniazid.
    • Diagnosis: Clinical; urinary N-methylnicotinamide.
    • Treatment: Niacin/Nicotinamide (e.g., 300-500 mg/day).

⭐ Hartnup disease, an autosomal recessive disorder affecting neutral amino acid transport (including Tryptophan), can lead to Pellagra-like symptoms due to impaired Niacin synthesis.

  • Toxicity (Excess):
    • Niacin flush: Prostaglandin-mediated (PGD2); ↓ with aspirin.
    • Peptic Ulcer Disease (PUD), Gout, Hepatotoxicity.
  • Therapeutic Uses (Pharmacological Doses):
    • Hyperlipidemia: ↓ LDL, ↓ TGs, ↑ HDL.
      • Mechanism: Inhibits VLDL synthesis & adipose tissue lipolysis.
      • Dose: 1-3 g/day.

High‑Yield Points - ⚡ Biggest Takeaways

  • Niacin (B3) is precursor for coenzymes NAD+ & NADP+, vital in redox reactions.
  • Deficiency causes Pellagra: the 3 Ds (Dermatitis, Diarrhea, Dementia).
  • Tryptophan is a precursor (60:1 ratio); deficiency seen in Hartnup disease & carcinoid syndrome.
  • NAD+ is key in catabolism (e.g., glycolysis); NADPH (from NADP+) in anabolism (e.g., FA synthesis) & antioxidant defense.
  • Therapeutic doses treat hyperlipidemia; common side effect is flushing.

Practice Questions: Niacin and NAD/NADP

Test your understanding with these related questions

A 45-year-old man presents with the following skin changes (as shown in the image). What relevant history should be taken to diagnose this condition?

1 of 5

Flashcards: Niacin and NAD/NADP

1/10

Vitamin _____ excess is associated with hyper-glycemia and hyper-uricemia

TAP TO REVEAL ANSWER

Vitamin _____ excess is associated with hyper-glycemia and hyper-uricemia

B3 (niacin)

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial