Metabolism of Tryptophan
(tryptophan is an essential amino acid)
- Tryptophan is used for:
- Protein synthesis
- Serotonin and Melatonin synthesis
- NAD⁺ / NADP⁺ synthesis
- Production of Kynurenine and related metabolites
- Initial Step:
- Tryptophan is converted to Kynurenine
- Enzyme: Tryptophan dioxygenase
- Requires Vitamin B6 (pyridoxine) later in pathway
Synthesis of NAD⁺ (Niacin) from Tryptophan
- About 60 mg Tryptophan → 1 mg Niacin (Vitamin B3).
- Pathway:
- Tryptophan → Kynurenine → 3-Hydroxykynurenine → Quinolinic Acid → NAD⁺
- Cofactors Required:
- Vitamin B6 (pyridoxine)
- Vitamin B2 (riboflavin)
- Iron
- Importance of NAD⁺ / NADP⁺:
- NAD⁺ used in catabolic oxidation reactions (ATP production)
- NADP⁺ used in anabolic reactions such as fatty acid and steroid synthesis
Clinical Link: Pellagra
- Occurs in niacin deficiency or tryptophan deficiency.
- Causes:
- Poor diet (corn-based diet)
- Carcinoid syndrome (tryptophan diverted to serotonin)
- Vitamin B6 deficiency (pathway blocked)
- Symptoms: 3 D’s
- Dermatitis
- Diarrhea
- Dementia
- (4th D: Death if untreated)
Synthesis of Serotonin and Melatonin from Tryptophan
Serotonin (5-Hydroxytryptamine)
- Tryptophan → 5-Hydroxytryptophan
- Enzyme: Tryptophan hydroxylase
- Requires BH4 (tetrahydrobiopterin)
- 5-Hydroxytryptophan → Serotonin
- Enzyme: Aromatic amino acid decarboxylase
- Requires Vitamin B6
- Sites of Serotonin Production:
- GI enterochromaffin cells (90%)
- Brain (raphe nuclei)
- Platelets (storage)