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1. BIOCHEMISTRY
[B. Pharm – I Yr.]
Topic: Catabolism of phenylalanine and tyrosine
Umesh Kumar
Assistant Professor
Dept. of Pharm. Chemistry
Hygia Institute of Pharmaceutical Education and Research

2. Catabolism of phenylalanine and tyrosine
• Phenylalanine (Phe, F) and tyrosine (Tyr, Y) are structurally related aromatic amino acids.
• Phenylalanine is an essential amino acid while tyrosine is non-essential. Besides its incorporation
into proteins, 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.
• 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.
• During the course of degradation, phenylalanine and tyrosine are converted to metabolites which
can serve as precursors for the synthesis of glucose and fat. Hence, these amino acids are both
glucogenic and ketogenic.

4. DEGRADATION OF TYROSINE (PHENYLALANINE)

5. DISORDERS OF TYROSINE
(PHENYLALANTNE) METABOLTSM

6. 1. PHENYLKETOUREA (PKU)
• Phenylketonuria (PKU) is the most common metabolic disorder in amino acid metabolism.
• The incidence of PKU is 1 in 10,000 births.
• It is due to the deficiency of the hepatic enzyme, phenylalanine hydroxylase, caused by an
autosomal recessive gene.
• The net outcome in PKU is that phenylalanine is not converted to tyrosine.
Phenylalanine metabolism in PKU
• Phenylketonuria primarily causes the accumulation of phenylalanine in tissues and blood, and
results in its increased excretion in urine.
• Due to disturbances in the routine metabolism, phenylalanine is diverted to alternate pathways,
resulting in the excessive production of phenylpyruvate, phenylacetate, phenyllactate and
phenylglutamine.
• AII these metabolites are excreted in urine in high concentration in PKU. Phenylacetate gives the
urine a mousey odour

7. Conti……
• The name phenylketonuria is coined due to the fact that the metabolite phenylpyruvate is a keto acid
(C6H5CH2-CO-COO-) excreted in urine in high amounts.

8. Clinical/biochemical manifestations of PKU
• The disturbed metabolism of phenylalanine resulting in the increased concentration of phenylalanine
and its metabolites in the body causes many clinical and biochemical manifestation-
1. Effects on central nervous system- Mental retardation, failure to walk or talk, failure of growth,
seizures and tremor are the characteristic findings in PKU. If untreated, the patients show very low
IQ (below 50).
2. Effect on pigmentation- Melanin is the pigment synthesized from tyrosine by tyrosinase.
Accumulation of phenylalanine competitively inhibits tyrosinase and impairs melanin formation.
The result is hypopigmentation that causes light skin colour, fair hair, blue eyes etc.
Treatment of PKU
• The maintenance of plasma phenylalanine concentration within the normal range is a challenging task
in the treatment of PKU.
• This is done by selecting foods with low phenylalanine content and/or feeding synthetic amino acid
preparations, low in phenylalanine.
• Early diagnosis (in the first couple of months of baby's life) and treatment for 4-5 years can prevent
the damage to brain.
• In some seriously affected PKU patients, treatment includes administration of 5-hydroxytryptophan
and dopa to restore the synthesis of serotonin and catecholamine.

9. 2. TYROSINEMIA
Tyrosinemia Type II
• This disorder-also known as Richner Hanhart syndrome, is 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, phydroxy phenylacetate, N-acetyltyrosine-and tyramine are observed.
• Tyrosinemia type II is characterized by skin (dermatitis) and eye lesions and, rarely, mental retardation.
• A disturbed self-coordination is seen in these patients
Tyrosinosis or Tyrosinemia Type I
• This is due to the deficiency of the enzymes fumarylacetoacetate hydroxylase and/or maleylacetoacetate
isomerase.
• Tyrosinosis is a rare but serious disorder. It causes liver failure, rickets, renal tubular dysfunction and
polyneuropathy.
• Tyrosine, its metabolites and many other amino acids are excreted in urine. In acute tyrosinosis, the infant exhibits
diarrhea, vomiting, and 'cabbage-like' odor.
• Death may even occur due to liver failure within one year. For the treatment, diets low in tyrosine, phenylalanine
and methionine are recommended.

10. 3. Albinism
• Albinism (Greek: albino-white) is an inborn error, due to the lack of synthesis of the pigment melanin.
• It is an autosomal recessive disorder with a frequency of 1 in 20,000.
• The most common cause of albinism is a defect in tyrosinase, the enzyme most responsible for the
synthesis of melanin.
Clinical manifestation
• 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.
• However, there is no impairment in the eyesight of albinos.

11. Synthesis of Catecholamines

12. • The name catechol refers to the dihydroxylated phenyl ring The amine derivatives of catechol are
called catecholamines
• Tyrosine is the precursor for the synthesis of catecholamines, namely dopamine, norepinephrine
(noradrenaline) and epinephrine (adrenaline).

14. THANK YOU
HYGIA GROUP OF INSTITUTIONS
GHAILA ROAD, GAAZIPUR BALRAM,
FAIZULLAHGANJ, LUCKNOW