Tryptophan

• Tryptophan is an essential amino acid.
• It contains indole ring.
• It is α- amino and β- indole propionic acid.
• Tryptophan is both glucogenic and ketogenic in nature.
• Substances produced from tryptophan are-

1. Alanine
2. Acetoacetyl CoA
3. Formyl group
4. Niacin and NAD+
5. Serotonin
6. Melatonin

Metabolism of tryptophan is divided into 2 –

1. Kynurenine (kynurenine- anthranilate pathway)
2. Serotonin pathway

A. Kynurenine pathway (Catabolic pathway Tryptophan)

• This pathway mostly occurs in liver.
• Tryptophan is oxidised to kynurenine by enzyme Tryptophan pyrrolase, which is then converted to either niacin or acetyl- CoA. Alanine also produced.
• Kynureninase is an enzyme dependent on pyridoxal phosphate.
• So, in Vitamin B6 deficiency, the pathway is blocked leading to niacin deficiency which causes pellagra.
• In pyridoxal deficiency, Xanthurenic acid is excreted in urine. 

B. Serotonin Pathway-

• It is called as 5 Hydroxytryptamine)
• It is neurotransmitter, synthesized from tryptophan.
• It is synthesized in brain, mast cells, platelets, and gastrointestinal mucosa.
• Tryptophan is first oxidized to serotonine which is further converted to melatonin.

Functions of Serotonin-

• Neurotransmitter in the brain
• Controls behavioural pattern
• GI motility
• Temperature regulation
• Potent vasoconstrictor
• Serotonin secretion is increased in carcinoid syndrome which causes flushing, Vasoconstriction, diarrhea and bronchospasm. 

      Melatonin-

• Melatonin is a hormone, mostly synthesized by the pineal gland.
• Functions of Melatonin-
• Diurnal variation
• Biological rhythm
• Sleep wake cycle

Metabolic Disorders associated with Tryptophan Metabolism-

1. Carcinoid syndrome
2. Hartnup’s Disease
3. Blue Diaper Syndrome  

 Hartnup’s disease-

• It is autosomal recessive condition.
• Defective absorption of tryptophan and other neutral amino acid from intestine and renal tubules.
• Decreased synthesis of niacin and serotonin.

Clinical features-

• Asymptomatic
• Cutaneous Photosensitivity
• Pellagra like symptoms.
• Neurological symptoms

Diagnosis-

• Obermeyer Test

Treatment-

• High protein diet
• Nicotinic acid or nicotinamide

• Specialized products from tryptophan are- Niacin, Seratonin, Melatonin
• 60 mg Tryptophan is converted to 1 mg of Niacin.
• Pellagra Like Symptoms in Hartnup’s Disorder- 
• Decreased absorption of Tryptophan from intestine.
• Decreased availability of Trp for NAD’ pathway leading to Niacin deficiency.