Tryptophan Metabolism

1. Tryptophan Metabolism
Dr. Ashok Kumar J
International Medical School
Management and Science University
Malaysia

2. Tryptophan
•Aromatic amino acid
•Essential amino acid
•Glucogenic and ketogenic
Dr Ashok Kumar J
Professor: Department of Biochemistry
2
Indole group
COO-NH3
CH
CH2
OH
NH

3. Tryptophan
Serotonine
Neurotransmitter
Melotonin
Neurotransmitter
Alanine
Glucogenic
Niacin – NAD+
(60mgs of tryptophan required to
form 1mg of Niacin)
Vitamin - coenzyme
Formyl group is released
One carbon compound
Acetoacetyl CoA
Ketogenic

4. Tryptophan
O2
Tryptophan Pyrrolase
N- Formyl kynurenine
THFA
Kynurenine Formylase
Kynurenine
Formyl THFA
O2
3- OH Kynurenine
3-OH Anthranilic acid
Kynureninase; PLP
Acetoacetyl CoA
Alanine
NAD+
(Co-enzyme form of Niacine)
Dr Ashok Kumar J
Professor: Department of Biochemistry
Kynurenine
Hydroxylase
4

5. Tryptophan
3- OH Kynurenine
Kynureninase; PLP
Xanthurenic acid
excreted in urine
Deficiency of niacin leads to decreased - PLP
3-OH Anthranilic acid
Xanthurenic acid
Dr Ashok Kumar J
Professor: Department of Biochemistry
Coenzyme form of water
soluble vitamin niacin is PLP
NAD+ Alanine Acetoacetyl CoA

6. Vitamin B6
deficiency
Kynureninase
function defective
3 – OH kynurenine
accumulates
3 – OH kynurenine is
converted to
XANTHURINIC ACID
-Excreted in urine
Normal person
excretes 1 to 3 mgs
of xanthurenic acid
in urine/day
2 to 11 mg in 24
hour urine after
taking a 2 gram load
of tryptophan
In pyridoxine
deficiency much higher
amount of xanthurenic
acid is excreted after
loading with
tryptophan –
up to 60 mgs/day

7. Pellagra like symptoms in maize eating
population is due to tryptophan deficiency
Dr Ashok Kumar J
Professor: Department of Biochemistry
7
60 mg of tryptophan forms 1 mg of niacin
Tryptophan rich diet has sparing effect on
niacin requirement

8. Tryptophan
Indolpyruvic acid
Indoleacetic acid
Sketol
Transaminase
Degradation of
tryptophan
Intestinal bacterial
putrifaction of tryptophan
Produce various indole
compounds
Excreted in feces as
sketoxyl
In urine as indoxyl and and
indican
Indole
Dr Ashok Kumar J
Professor: Department of Biochemistry
8
Indoxyl Indoxyl sulfate Indican

9. SERETONIN
Synthesized from tryptophan
(1% of tryptophan converted to serotonin)
Present in
Gastric mucosa
Intestine
Brain
Mast cells
Platelets
Synthetic reaction is similar to synthesis
of dopamine

10. Tryptophan
O2
5-OH Tryptophan
5-OH Tryptamine
(Serotonine)
H2O
Tryptophan Hydroxylase
Decarboxylase :PLP
Tetrahydobiopterin
Dihydobiopterin
CO2
Dr Ashok Kumar J
Professor: Department of Biochemistry
Synthesis of
serotonin from
tryptophan
10

11. Serotonin
Does not
cross Blood
Brain Barrier
serotonin
Is locally
produced in
the brain
serotonin
Acts as a
neurotransmitter

12. Serotonin Functions
Neurotransmitter : Regulation of cerebral activity
(Stimulate), Controls the behavioral pattern, sleep,
blood pressure and body temperature
Evokes release of peptide hormones from GIT:
Increases gastric motility
Powerful vasoconstrictor – smooth muscle constriction
in bronchioles and arterioles
Sensitivity to pain is reduced

13. Serotonin
When protein rich diet taken – all amino acids are
available in blood
Cause traffic jam I the amino acid transport system in
brain
Tryptophan bulkiest amino acid - taken very slowly
When carbohydrate rich diet is taken – insulin
secretion is increased
Lower the amino acid concentration in the blood
Tryptophan easily enters the brain – serotonin
production increased – induce sleep

14. 5-OH Tryptamine
(Serotonine)
Monoamine
Oxidase (MAO)
5-OH Indole acetic acid
(5HIAA)
5 – OH Indole acetic
acid excreted in urine
Levels of serotonin have been linked to
mood, many antidepressant drugs were
developed that affect serotonin levels
Inhibitors of MAO :
decrease the degradation of
serotonin:
Serotonin concentration increases
Excess production of
Serotonine – Increased
excretion of 5-HIA

15. • Inhibits MAO
• Elevates serotonin concentration
• Psychic stimulation
Iproniazide
•Competes with serotonin
•Acts as depressant
Lysergic acid
diethylamide (LSD)

16. • Increases degradation of
serotonin Reserpine
• Part of the serotonin released is
again taken up
• Selective serotonin reuptake
inhibitors (SSRI) – used in the
treatment of psychiatric disorders
fluoxetine

17. Carcinoid Syndrome

18. Argentaffin cells
Serotonin producing cells of
intestine
Uncontrolled growth develops –
tumor called malignant carcinoid
( argentaffinoma)
Normally 1% of Tryptophan
converted to serotonin
Carcinoid syndrome – 60% of
tryptophan diverted to serotonin
production
Normal tryptophan metabolism is
affected
Synthesis of NAD+ is impaired –
symptoms of Pellegra
Serotonin synthesis increase (>40mg/dl)
Cutaneous flushing
Respiratory distress
Bronchospasm
Right sided heart failure
Fluctuating hypertension

19. Urinary excretion of 5 HIAA is increases
Urine collected after stopping all
medications for 72 hours
Dietary sources of 5-HIAA like
• banana
• red plum
• pineapple
• tomatoes
• cough syrup with glycerol guaiacolate
• drugs like indomethacin
should be avoided for few days before
urine collection
Random fresh urine sample
collected
• Normal excretion is 2 – 7 mg/day
• If urine level is > 25 mg/ day
diagnosis of carcinoid tumor
• In metastatic carcinoid tumor -
up to 350mg/day
•

20. First described in the Harnup’s
family – so the name
Impaired transport of
tryptophan and neutral amino
acids in intestine, renal
tubules
Mental retardation
Intermittent cerebellar ataxia
Pellegra like skin rashes
Plasma level of tryptophan is
decreased
Urine excretion of tryptophan,
indole compounds increased
Decreased synthesis of serotonin
and niacin are responsible for
neurological symptoms and pellagra
like rash
Hartnup’s Disease

21. Acetylated and methylated to form melatonin
Acetyl CoA
CoA
Acetyl
Serotonine
SAM
SAH
Melatonin
Acetyalse
Methyl
transferase
Serotonine

22. Functions of Melatonin
Produced in Pineal gland
in response to the light–dark cycle
level in the blood rising in a dark environment
Action is thought to be mediated via c AMP
Connected with the diurnal variations, sleep wake cycles
involved in regulating reproductive functions.

23. Dr Ashok Kumar J
Professor: Department of Biochemistry
23
Thank You