Learning Objectives
- Identify NAD+ and NADP+ as the active forms of Niacin.
- Explain the de novo synthesis of Niacin from Tryptophan and the required cofactors (B2, B6).
- Recognize the “3 D’s” of Pellagra and its diverse etiologies.
- Contrast the side effects of Niacin excess, including prostaglandin-mediated flushing.
1. Biochemical Function & Synthesis
Niacin (Vitamin B3) is essential for energy metabolism. It is a constituent of NAD+ and NADP+, which serve as electron carriers in redox reactions.
- Synthesis: Derived from the amino acid Tryptophan. This process requires Vitamin B2 (Riboflavin) and Vitamin B6 (Pyridoxine).
- Therapeutic Use: Used to treat dyslipidemia by decreasing VLDL and significantly increasing HDL.
Memory Hook: NAD is from Niacin (B3 yields ~ 3 ATP).
Activity
2. Deficiency: Pellagra and the “3 D’s”
Severe deficiency leads to Pellagra. While dietary lack is one cause, several other conditions can precipitate this state:
| Symptom (The 3 D’s) | Clinical Presentation |
|---|---|
| Dermatitis | Hyperpigmentation of sun-exposed areas; Casal necklace (C3/C4 broad collar rash). |
| Diarrhea | Due to atrophy of the columnar epithelium of the GI tract. |
| Dementia | Includes hallucinations and cognitive decline. (The 4th “D” is Death). |
Secondary Causes of Pellagra:
- Hartnup Disease: AR deficiency of neutral amino acid transporters (Tryptophan) in the kidneys and gut.
- Malignant Carcinoid Syndrome: Increased Tryptophan consumption to synthesize excess Serotonin.
- Isoniazid (INH) Therapy: Depletes Vitamin B6, which is required for Niacin synthesis.
3. Niacin Excess (Toxicity)
High doses of Niacin used for lipid control can cause significant side effects.
- Facial Flushing: Induced by Prostaglandins (not histamine). Taking Aspirin 30 minutes before Niacin can prevent this.
- Metabolic Effects: Can cause hyperglycemia (insulin resistance) and Hyperuricemia (may precipitate Gout/Podagra).
Activity
Activity