Metabolism of Tryptophan and its disorders.

2. Tryptophan is ….
Aromatic AA
Indole ring.
α-amino β-indole propionic acid
Neutral A.A .
Essential A.A. (first to be identified as an essential AA.)
Both Glucogenic and Ketogenic .

5. Metabolism of tryptophan is divided into
Kynurenine Pathway
Serotonin Pathway.

6. Mainly takes place in Liver.
Through this pathway, tryptophan is oxidized to
Alanine (enter in gluconeogenesis)
Acetyl CoA (used for the synthesis of lipids)
Niacin coenzymes (NAD+, NADP+)

7. Kynurenine
Pathway
Tryptophan
Tryptophan Oxygenase
Formylkynurenine
Kynurenine
3-Hydroxykynurenine
3-Hydroxyanthranilate
Acetyl CoA
Quinolinate
Niacin
Xanthurenate
Excreted
in urine
O2
Fe++
Kynurenine formylase
H2O
Formyl
Kynurenine
hydroxylase
O2
NADPH+H+
Kynureninase H2O
Alanine
PLPDeficiency of vitamin B6
One ‘C’
pool
Glucogenic
pathway
Ketogenic
pathway
NAD &
NADP
synthesis
The enzyme kynurenine
hydroxylase is
inhibited by estrogen,
hence women, in
general, are more
susceptible to pellagra.

8. Serotonin or 5-hydroxytryptamine (5HT)
It is a neurotransmitter
Normally, about 1% of the tryptophan is
converted to serotonin.
Is widely distributed in the body.
In mammals, the largest amount is synthesized in
the intestinal cells.
The formation of serotonin is comparable with
the production of catecholamines.

9. Tryptophan
Tryptophan
hydroxylase
5-Hydroxytryptophan
5-Hydroxytryptamine
(Serotonine)
N-Acetylserotonine
N-Acetyl-5-
methoxyserotonine
(melatonine)
H4-biopterin
Decarboxylase
5-Hydroxyindoacetic
acid
Acetyl transferase
Methyl transferase
CO2
Acetyl CoA
CoA-SH
SAM
MAO
Pineal gland
S-Adenosyl
homocystein

10. 5-Hydroxytryptamine
(Serotonine)
5-Hydroxyindoacetic
acid
Monoamine
Oxidase (MAO)
Urine

11.  Excitatory Neurotransmitter in brain (antidepressant)
It is closely involved in the regulation of cerebral
activity (excitation).
Potent Vasoconstrictor and causes Smooth muscle
contraction in bronchioles and arterioles.
Enhances Platelet aggregation.
Causes Peristalsis, peptide hormone release in GIT.
Serotonin controls the behavioural patterns, sleep,
blood pressure and body temperature

12. Excitatory Neurotransmitter in brain
(antidepressant)
It involved in various Behavior patterns -
Sleep,
Social,
Mood,
 Pain,
Appetite,
Temperature regln.
 Serotonin level is found to be low in
patients with depressive psychosis.

13. Carbohydrates will induce sleep,
while protein rich foods will cause
alertness

14. Serotonin is produced by argentaffin cells
of GI tract.
When these cells undergo uncontrolled
growth.
Leads to Carcinoid Syndrome (Argentaffinomas)
 Serotonin ( 60% of Tryptophan – Serotonin)
 Flushing, Sweating, Broncho- constriction,
Diarhoea, Heart Failure .
 Tryptophan to Niacin - Pellagra .
  5-HIAA in urine (<5mg to upto500mg/day)

15. It is hormone produced by Pineal gland.
Synthesis is regulated by light-dark cycle.
Also functions as Neuro-transmitter
Modulates Circadian rhythm
Sleep-Wake cycle
Regulates Reproductive function .
Blocks MSH, ACTH actions.

18. This disorder was first described in
the family of Hartnup.
Genetic: An autosomal recessive disorder.
Defect: intestinal & renal transport of tryptophan
and other neutral amino acids (Ala, Ser,Val,His),
The net outcome: low levels of these AAs in the
blood and their  excretion in urine.
Diagnosis: ↑ Indican in urine, ↓ plasma Tryptophan.

19. Urinary loss leads to tryptophan deficiency.
The clinical symptoms include dermatitis, ataxia,
mental retardation, Neutral Aminoaciduria etc.
Pellagra-like and neurological symptoms are common
in these patients due to…
Impairment in the synthesis of NAD+ and serotonin
from tryptophan.

20. ….