For All Medical & Non Medical Students

1. 1
By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH

2. 2

3. Metabolic fate
Tyrosine
Phenylalanine
Fumarate Glucose
Acetoacetate Fat
Synthesis of
Melanin pigment

4. 4
Synthesis of
Melanin
Melanin Polymers
(Black)
pigment of skin,
hair and eye
containing oxygenase)

5. 5
Melanin is the pigment of skin, hair and eye.
Tyrosine is the precursor for melanin and only one enzyme, namely tyrosinase (cu-
containing oxygenase), is involved in its formation.
Tyrosinase hydroxylates tyrosine to form DOPA (3, 4-dihydroxyphenylalanine)
The next reaction is also catalysed by tyrosinase in which DOPA is converted to
Dopaquinone.
Dopaquinone is spontaneously converted to Leucodopachrome followed by 5, 6-
dihydroxyindole.
The oxidation of 5, 6-dihydroxyindole to indole 5, 6-quinone is catalysed by
tyrosinase, and DOPA serves as a cofactor.
Melanochromes are formed from indole quinone, which on polymerization are
converted to black melanin.

6. due to the lack of synthesis of the
pigment melanin
Deficiency of the enzyme tyrosinase
Decrease in melanosomes of melanocytes
Impairment in melanin polymerization
Biochemical basis
ALBINISM

7. Lack or protein matrix in melanosomes
Limitation of substrate (tyrosine) availability
Lack of melanin in albinos makes them sensitive to
sunlight
Increased susceptibility to skin cancer
Photophobia (intolerance to light) is associated with lack of pigment in the
eyes

8. Metabolic fate
Tyrosine
Phenylalanine
Biosynthesis of
Thyroid hormones
Fumarate Glucose
Acetoacetate Fat
Synthesis of
Melanin pigment

9. Biosynthesis
and
functions
of
Thyroid hormones
9

10. Thyroid hormones synthesized from the tyrosine residues of the protein
thyroglobulin and activated iodine.
L- Tyrosine
Thyroxine (T4)
Di-iodotyrosine
Mono-iodotyrosine +
Mono-iodotyrosine + Di-iodotyrosine Tri-Iodo
tyroxine (T3)
2 Di-iodotyrosine
Iodine
Coupling
Coupling
Iodination

11. Regulates the rate of metabolisms (CH’s,
Lipids & Proteins)
Maintenance of blood pressure
Maintain growth & development
Regulates enzyme activity system
Involved reproductive capabilities
Increased metabolic rate (Calorigenic effect)
Functions
The protein thyroglobulin
undergoes proteolytic
breakdown to release the
free hormones, T3 and T4.

12. Metabolic fate
Tyrosine
Phenylalanine
Thyroid hormones
Fumarate Glucose
Acetoacetate Fat
Melanin pigment
Biosynthesis of
Catecholamines
Dopamine (CNS)

13. 13
Biosynthesis
of
Catecholamines

14. 14
Vitamin-C, Cu2+

15. 15
The conversion of tyrosine to catecholamines occurs in adrenal medulla
(Dopamine, Norepinephrine & Epinephrine (adrenaline)
Tyrosine is hydroxylated to 3, 4-dihydroxy-phenylalanine (DOPA) by Tyrosine
hydroxylase.
DOPA undergoes PLP-dependent decarboxylation to give Dopamine which, in
turn, is hydroxylated to produce Norepinephrine.
Methylation of norepinephrine by SAM gives Epinephrine.

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Clinical Importance
of
Catecholamines

17. • Dopamine is also neurotransmitter (in extra pyramidal tract,
substantia nigra and striatal tract) and inhibits prolactin secretion
• Dopamine is mood regulator
Decreased Dopamine Increased Dopamine
Parkinsonism,
- Neurological disorder,
- Tremors,
- Slow voluntary movements
Treated With
drugs like Levo-DOPA,
carbidopa and Estrogen
Schizophrenia, (long term mental
disorder)
- Behavior changes,
- Negative thinking,
-Split personality due to excess firing
Treatment
- life long medication

18. Nor-epinephrine
inhibits neurotransmitter involves in
sympathetic nerve impulse transmission

19. Causes smooth muscle relaxation of bronchi & relief in
Asthma patients
Increases rate & force of myocardial contraction &
increases BP
Used as therapeutic drug
Epinephrine (Adrenaline)
Opposite to insulin increases gluconeogenesis and lipolysis
Releases on response to fight, fear, & flight

20. Catabolism of Catecholamines
(Dopamine, Nor-epinephrine, epinephrine)
• Epinephrine half life is only 2-5min.
• VMA is excreted in urine
• Normal level of excretion of VMA is 2
to 6mg/day
• More in excess metabolism of
epinephrine (pheochromocytoma)
and nor epinephrine (neuroblastoma).
Oxidatively
deaminate
3-OH-4-methoxymandelic acid

21. VMA Estimation
• to detect excess epinephrine and norepinephrine in urine.
• It is used to detect tumors called pheochromocytoma (Adrenal glands tumor),
Patient Preparation:
1. Collect a 24-hour urine specimen.
2. Add 25 mL of 50% acetic acid as preservative at the start of collection.
3. Advised to avoid chocolate, coffee, banana, venilla ice and citrus and drugs like
aspirin and antihypertensive medicines , produced more VMA in urine during test.
4. Decreased VMA levels may be seen in patients with uremia, alkaline urine, and
radiographic contrast media and drugs like phenothiazine, reserpine, guanethidine,
monoamine oxidase inhibitor, and disulfiram

22. • VMA id extracted by ethyl acetate.
• It is oxidized with metaperiodate to converts VMA to Vanillin.
• This is extracted with toluene form red color at 360nm.
• Methodology: Liquid chromatography/tandem mass spectrometry
(LC/MS-MS) & ELISA method
• VMA is also estimated by antibody method

23. Purpose Of The Test (Indications)
• To diagnose pheochromocytoma(Adrenal glands tumor ),
• VMA is of value for evaluation of hypertension,
• Also diagnose and follow up Neuroblastoma,
Ganglioneuroma, and
Ganglioneuroblastoma.
• Decreased VMA Level Is Seen In Diabetes & Parkinsonism.

24. Homovanilic acid (HVA) In urine
• It is also called methoxy-hydroxy phenyl acetic
acid
• It is main urinary metabolite of DOPA and
Dopamine while VMA is of the norepinephrine
pathway
• 24hr urine for this test
• Avoid drugs like L-dopa, disulfiram
• Increased in neuroblastomas,
pheochromocytoma and ganglioneuroma
• VMA/HVA ratio more than 1 has better
prognosis

25. Case Based Question-1
Two month old baby girl was brought by her parents for consultation.
She had pale skin, blonde hair and pink iris. The baby girl was otherwise
healthy, feeding well but was unable to fix the gaze. Parents revealed
that their first two children, a boy and girl, had complete albinism, but
the parents themselves were normal.
The eye examination of the child showed absence of pigment in the
retina
Q:
a. What is the probable diagnosis?
b. What is the biochemical abnormality of this disease?

26. Case Based Question-2
A 25years old man came to hospital with complain of photophobia,
and nystagmus (rapid involuntary movements of the eyes). He has
hypopigmented skin, hair and eye
Q:
a. What is the probable diagnosis?
b. Name the deficient enzyme of this disease?
c. Describe the biochemical basis of the symptoms observed in old
man
Rajesh K. Jambhulkar & Abhijit D N. Case Oriented Approach in Biochemistry:2019; p30

27. Case Based Question-3
A full term baby born to normal & healthy parents was found to have
marked lack of pigmentation. The baby had white hair, blue eyes and
depigmented skin. There was no impairment in the eyesight of baby.
However baby was unable to tolerate light (photophobia). The paternal
grandfather of the baby had similar problem.
Q:
a. What is the probable diagnosis?
b. Name the deficient enzyme causing the disease?
c. Describe the biochemical basis of the symptoms observed in child
Rajesh K. Jambhulkar & Abhijit D N. Case Oriented Approach in Biochemistry:2019; p31

28. Question-4
A full term infant was observed to have a lack of pigmentation, blue
eyes, white hair and confirmed as a case of albinism
Q:
a. What is the probable diagnosis?
b. Name the enzyme responsible for this defect?
c. Write biochemical reaction catalyzed by the enzyme ?
d. Name the amino acid, from which the pigment is synthesized
Pankaja Naik. Protein Metabolism. Biochemistry. 4th ed :2016; CH-3:p299

29. Case Based Question-5
A 15years old man with 2years history of refractory hypertension and
occasional panic attacks reported to the clinic with sudden episode of
pounding headache. There was excessive sweating. He had similar
attacks earlier. Family history is positive for hypertension. On
examination BP was 170/90mmHg and Pulse was 72/min. weight was
80kg. He was taking beta blockers. Other examination findings were
unremarkable. 24hr VMA was elevated (12mg/day)
Q:
a. What is the probable diagnosis?
Vasudevan DM, Kumar Das S . Aromatic & Heterocyclic amino acid. Text book of Biochemistry:Case-17.1:p321

30. Case photography
Q: a) What is the probable diagnosis?
b) Mention the biochemical defect

31. Next presentation on
AAM-6c:
Metabolism of Aromatic amino acids
(Catabolism , Metabolic fate & disorders
of Tryptophan
31
Thank you
have a good day