For All Medical & Non Medical Students

1. METABOLISM OF
AROMATIC AMINO ACIDS
By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH

2. Benzene group
Indole ring
Phenol group
Neutral, nutritionally essential,
metabolically both glucogenic and
ketogenic amino acid
Neutral, nutritionally non essential,
metabolically glucogenic & ketogenic amino
acid
Neutral, Nutritionally essential,
metabolically both Glucogenic & ketogenic
amino acid

3. AAM 06c: CATABOLISM OF
TRYPTOPHAN
Neutral, Nutritionally essential, Metabolically
both Glucogenic & ketogenic a.a

4. TRYPTOPHAN
Alanine Glucose
Acetyl CoA Fat
Synthesis of Niacin (B3)
Formation of Melatonin
Biosynthesis of Serotonin
Formyl group (one“C” pool)
Excretory products
(5 –OH IAA, Indican)

5. Serotonin pathway
Kynurenine pathway
Tryptophan catabolized by two ways
Kynurenine Alanine
Niacin Acetyl Co-A
Serotonin
Melatonin 5-HIAA

6. Kynurenine
pathway

7. Tryptophan
L-Formylkynurenine
3-OH Kynurenine
3-OH Anthranilic acid
L-Kynurenine
Tryptophan dioxygnase /
Pyrrolase (Fe2+)
Kynurenine formylase
Kynurenine hydroxylase
Kynureninase
PLP
O2
O2
H2O
Formyl- group
One Carbon pool
NADPH + H+
Acetyl CoA
Alanine
Glucogenic nature
Ketogenic
Niacin
NAD + & NADP+ Decarboxylation
3%
60mg of try=1mg of
Niacin
NADH & NADPH

8. Deficiency of Vit-B6
(pyridoxine)
Normal excreted in urine 1-3mg/day
But vitB6 def excreted 3-11mg/day
Greenish blue / yellow urine

9. Serotonin Pathway

10. Serotonin (Biological amine) synthesized by brain, mast cells,
GIT mucosa, neurons, pineal gland,
(5-HT)
5-OH tryptamine
NADPH
NADP+
1-3% Tryptophan daily used to synthesis of serotonin

11. Functions of Serotonin
• Powerful neurotransmitter in brain,
• Potent vasoconstrictor
• Stimulator of smooth muscle contraction
• Induces peristaltic movements
• Anti depressant
• Serotonin is Pain reducer

12. 12
Oxidative deamination of serotonin by MAO
leads to form 5-HIAA- excreted free form
MAO inhibitors used in treatment of
psychiatric disorders (Iproniazid, tricyclic
antidepressants)
(Excreted form)
Degradation of serotonin

13. Clinical Significance Of Serotonin
• Plays imp role in depression and carcinoid tumors
• Involved in a variety of behavioral patterns like sleep, perception of
pain, social behavior, mental depression
• Decreased serotonin leads to depression
Treatment:
• Anti-depressant drugs (amitriptyline & trazodone),
• Results inhibit the reuptake of serotonin by presynaptic neurons-
• Increased conc. of serotonin at serotonergic synapses

14. Carcinoid Tumors (Argentaffinoma)
• Characterized by serotonin producing tumor cells in argentaffin
tissues of the abdominal cavity.
• Develop from enterochromaffin cells, distributed throughout the
GIT, biliary tract, gall bladder & pancreatic duct
• Up to 60% of Try is diverted to serotonin formation

15. Clinical symptoms:
– Pellagra may also seen
– Bronchial constriction,
– Diarrhea,
– Cardiac lesions associated with heart failure
• Increased urinary excretion of 5-OH Indolaceticacid

16. Diagnostic test:
• Measurement of urinary 5-HIAA conc.
• More than 25mg/day (normal 5-HIAA conc. is 2 to 7mg/day)
• Measurement of 5-HTP (5- OH tryptophan)

17. 17
Blocks MSH & ACTH
Synthesis of Melatonin
(Pineal gland)
Regulated by light dark cycle (mostly at night)

18. Functions of Melatonin
• It is sleep inducing substance
• Regulated by sleep-wake cycle
• Involved in regulation of circadian rhythm &
reproductive fraction of the body
• It is anti-ageing agent

19. Disorders
of
Tryptophan

20. Impaired transport of Try & neutral amino acids in
intestine & renal tubules
Defect limits tryptophan availability for niacin
synthesis & accounts for pellagra like symptoms.
Due to intestine bacteria try is metabolized to indol
acetic acid & indol pyruvic acid, excreted more in urine
Inherited disorder, Severity less in adult life
Hartnup’s disease

21. Cerebral Ataxia
Muscle Discomfort
Psychological Symptoms
Clinical features
Generalized neutral amino aciduria
Rashes, Diarrhoea

22. Increased urinary excretion of indican, indol acetic acid
& other indol derivatives
Oral tryptophan load produces an abnormal plasma Try
levels verses time curve.
Diagnosis
Indol derivatives in urine measured by Obermeyer test

23. Oral niacin supplement will permit adequate
syn of NAD+
This corrects pellagra like symptoms but amino
aciduria remains unaltered
Therapy

24. Case Based Question-01
A 12 year old boy had sudden onset of rashes, diarrhoea, and his school
performance was also decreased because of lose of memory. Laboratory
tests revealed aldehyde test with urine sample of the patient was
positive
Q A: Identify the inborn error and major defect
B: Mention the confirmatory qualitative test for this disorder
C: Which vitamin supplement required for the above condition
Wilma Delphine silvia et al. OSPE& CBL .Competency Based Practical Biochemistry Text book, 2nd ed.; case-8: p146

25. CBQ-2
A 3 year old boy was admitted to hospital with the symptoms of
pellagra, accompanied by mental retardation and excessive
excretion of neutral amino acids. He was diagnosed as having
hartnup’s disease.
Q A: What is the cause of this disease?
B: Why does it show mental retardation and pellagra like symptoms
C: How will you treat pellagra like symptoms ?
D. Can aminoaciduria be treated?
Textbook of biochemistry by Pankaja naik; p298

26. MCQs
Increased urinary indole acetic acid is diagnostic of ?
a. Maple syrup urine disease b. Hartnup disease
c. Phenylketonuria d. Homo cysteinuria
Absorption of which one of the following amino acids is defective in Hartnup disease
a. Lysine b. Leucine
c. Tyrosine d. Tryptophan
Malignant carcinoid is a metabolic disorder of ?
a. Lysine b. Leucine
c. Tryptophan d. Tyrosine
Pellagra is manifested in which conditions ?
a. Niacin deficiency b. Tryptophan deficiency
c. Malignant carcinoid d. Above all
Tryptophan is deficient in which food stuff ----------------

27. Next Presentation on
AAM-07: Metabolism of Sulphur containing
amino acids & its Disorders
Thank You
Have A Nice Day To All