UNIT III_Amino acid Metabolism.pptx

1. UNIT: III
Amino acid
metabolism
By Mrs. Sonali Nikam
Assistant professor
Faulty of Pharmaceutical Sciences

2. Content
• General reactions of amino acid metabolism: Transamination, deamination &
decarboxylation, urea cycle and its disorders
• Catabolism of phenylalanine and tyrosine and their metabolic disorders
(Phenyketonuria, Albinism, alkeptonuria, tyrosinemia)
• Synthesis and significance of biological substances; 5-HT, melatonin, dopamine,
noradrenaline, adrenaline
• Catabolism of heme; hyperbilirubinemia and jaundice

3. • Catabolism of phenylalanine and tyrosine
• Phenylalanine and tyrosine are aromatic amino acids.
•
• Phenylalanine is an essential amino acid while tyrosine is non-
essential
• Predominant metabolism of phenylalanine occurs through tyrosine.
• Tyrosine is incorporated into proteins and is involved in the Synthesis of a
variety of biologically important compounds - epinephrine,
norepinephrine, dopamine (catecholamines), thyroid hormones and the
pigment melanin

4. The only function of
Phenylalanine is its conversion to
tyrosine. For this reason, ingestion of
tyrosine can reduce the dietary
requirement of phenylalanine this
Phenomenon is referred to as 'sparing
action’ of tyrosine on phenylalanine.
Due to a defect in phenylalanine
hydroxylase, the conversion of
phenylalanine to tyrosine is blocked
resulting in the disorder phenylketonuria
(PKU).

5. Conversion of phenylalanine to tyrosine
• Phenylalanine is hydroxylated at para-position by phenylalanine hydroxylase to
produce tyrosine (p-hydroxy phenylalanine).
• Irreversible reaction.
• Requires specific coenzyme biopterin.
• Enzyme phenylalanine hydroxylase is present in the liver.
• Reaction involves the incorporation of one atom of molecular Oxygen (O2) into
the para position of phenylalanine

6. Degradation of Tyrosine (phenylalanine)
The metabolism of phenylalanine and tyrosine
is considered together the sequence of reactions occurs.

7. Transamination
Decarboxylation
awa hydroxylation
Cleave benzene ring
Isomerization
Hydrolysis

8. • Synthesis and significance of biological
substances; Melatonin
Melanin (Creek: melan-black) is the pigment of skin,
hair and eye.
The synthesis of melanin occurs in melanosomes
present in melanocytes, the pigment-producing cells.
Melanin-the colour pigment : The skin colour
of the individual is determined by the relative
concentrations of black and red melanins.
This in turn, is dependent on many factors, both
genetic and environmental.

9. The presence of moles on the body represents a
localized severe hyperpigmentation due to
hyperactivity of melanocytes.
On the other hand,
localized absence or degeneration of
melanocytes results in white patches on the
skin commonly known as leukoderma.
Albinism is an inborn error with generalized
lack of melanin synthesis.
Albinism (Greek: albino-white) is an inborn
Error due to the lack of synthesis of the
pigment melanin. lt is an autosomal recessive
disorder with a frequency of 1 in 20,000.

10. Many possible causes of albinism have been identified
1. Deficiency or lack of the enzyme tyrosinase.
2. Decrease in melanosomes of melanocytes.
3. impairment in melanin polymerization.
4. Lack of protein matrix in melanosomes.
5. Limitation of substrate (tyrosine) availability.
6. Presence of inhibitors of tyrosinase.

11. Tyrosinemia:
Richner- Hanhart syndrome.
due to a defect in the enzyme tyrosine transaminase.
The result is a blockade in the routine degradative pathway of tyrosine.
Accumulation and excretion of tyrosine and its metabolites-namely p-
hydroxyphenylpyruvate, p- hydroxyphenyllactate, phydroxyphenylacetate, N
acetyltyrosine -and tyramine are observed,
Characterized by skin (dermatitis) and eye lesions and, rarely, mental retardation A.
Disturbed self-coordination is seen in these patients.
Neonatal tyrosinemia
Absence of the enzyme p-hydroxyphenylpyruvate dioxygenase.

13. Clinical manifestations:
• The most important function of melanin is the protection of the body from sun
radiation.
• Lack of melanin in albinos makes them sensitive to sunlight.
• Increased susceptibility to skin cancer (carcinoma) is observed.
• Photophobia (intolerance to light) is associated with lack of pigment in the eyes.

14. • Synthesis and significance of biological substances; Catecholamines
• Catechol refers to the dihydroxylated phenyl ring and
the amine derivatives from catechol are called
catecholamine.
• Tyrosine is the precursor for the synthesis of
catecholamines, namely dopamine, norepinephrine
(noradrenaline) and epinephrine (adrenaline).
• Occurs in adrenal medulla and central nervous.
• Dopamine is predominantly synthesized in substantia
nigra and coeruleus of brain.
Catechol

15. • Hydroxylation
• Rate limiting step
• coenzyme
• Decarboxylation
• PLP dependant
• Hydroxylation
• Methylation

16. Hyperbilirubinemia
Hyperbilirubinemia is a condition in which there is a build up of bilirubin in
the blood, causing yellow discoloration of the eyes and skin, called
jaundice.
Hyperbilirubinemia is another term for jaundice.
Bilirubin is a molecule formed from the breakdown of heme, the iron-
containing, nonprotein component of hemoglobin.
Normal levels of bilirubin for older children and adults range from 0.3
to 1.0 mg/dL.
Clinically, elevated serum bilirubin levels manifest as jaundice, a
yellowing of the skin, sclera, and mucous membranes. Jaundice is
typically visible when the total serum bilirubin (TSB) is greater than
5 mg/dL

17. What causes hyperbilirubinemia?
During pregnancy, the placenta excretes bilirubin. When baby is born, baby’s
liver must take over this function. There are several causes of
hyperbilirubinemia and jaundice, including:
• physiologic jaundice: occurs as a “normal” response to your baby’s limited
ability to excrete bilirubin in the first days of life
• breast milk jaundice: about 2 percent of breastfed babies develop jaundice
after the first week
• breastfeeding jaundice: occurs in some baby’s in the first week due to low
intake or dehydration
• jaundice from hemolysis: a condition that results from the breakdown of red
blood cells due to hemolytic disease of the newborn (Rh
disease), polycythemia, or hemorrhage
• inadequate liver function: due to infection or other factors

18. Who is affected by hyperbilirubinemia?
About 60 percent of term newborns and 80 percent of premature babies develop jaundice.
Infants of diabetic mothers and of mothers with Rh disease are more likely to develop
hyperbilirubinemia and jaundice.
Why is hyperbilirubinemia a concern?
Although low levels of bilirubin are not usually a concern, large amounts can circulate to
tissues in the brain and may cause seizures and brain damage. This is a condition called
kernicterus.
What are the symptoms of hyperbilirubinemia?
Symptoms may include:
•yellow coloring of your baby’s skin (usually beginning on the face and moving down the
body) poor feeding or lethargy