This PPT contains topic related to Catabolism of Phenylalanine and Tyrosine, Disorders Of Tyrosine Metabolism and metabolic disorders like Phenyketonuria, Albinism, Alkaptonuria and Tyrosinemia. Books referred: https://www.amazon.in/s?k=satyanarayan+biochemistry&i=stripbooks&crid=2UMKA76J0R8WC&sprefix=satya%2Cstripbooks%2C456&ref=nb_sb_ss_i_2_5

2. • Phenylalanine and tyrosine are structurally related aromatic
amino acids.
• Phenylalanine: Essential amino acid
• Tyrosine: Non-essential amino acid.
• Only function of Phenylalanine is conversion to Tyrosine• Only function of Phenylalanine is conversion to Tyrosine
• Therefore, intake of tyrosine reduce the dietary requirement
of phenylalanine - ‘Sparing Action’ of Tyrosine on
Phenylalanine.

3. • Metabolism of phenylalanine occurs through tyrosine.
• Tyrosine is incorporated into proteins and helps in the synthesis of
epinephrine, norepinephrine, dopamine, thyroid hormones and
melanin.
• Phenylalanine and Tyrosine during degradation produce
metabolites, which are precursor for Fat and Glucose synthesis.metabolites, which are precursor for Fat and Glucose synthesis.
• That’s why these amino acids are both glucogenic and ketogenic.
• Phenylalanine and Tyrosine metabolism have special significance
for two reasons:
– synthesis of biologically important compounds.
– metabolic disorders due to enzyme defects.

5. Conversion of phenylalanine to tyrosine
• Irreversible reaction.
• Degradation of phenylalanine mostly occurs through
tyrosine.tyrosine.
• Phenylalanine is hydroxylated at para-position by
phenylalanine hydroxylase to produce tyrosine.
• Requires a specific coenzyme biopterin

6. • The active form of biopterin is tetrahydrobiopterin.
• In the phenylalanine hydroxylase reaction,
tetrahydrobiopterin is oxidized to dihydrobiopterin.
Tetrahydrobiopterin is then regenerated by an NADPH-
dependent dihydrobiopterin reductase.dependent dihydrobiopterin reductase.
• Defect in phenylalanine hydroxylase, blocks the
conversion of phenylalanine to tyrosine resulting in the
disorder phenylketonuria (PKU).

8. Degradation Of Tyrosine (Phenylalanine)
• The metabolism of phenylalanine and tyrosine
is considered together.
• The reactions of the degradation are• The reactions of the degradation are
described stepwise.

9. Step 1
• Single pathway is responsible for the
degradation of Phenylalanine & Tyrosine.
• Phenylalanine is converted to Tyrosine.• Phenylalanine is converted to Tyrosine.
• Occurs in liver.

10. Step 2
• Transamination Reaction.
• Tyrosine  p-hydroxyphenylpyruvate by
“tyrosine transaminase”“tyrosine transaminase”
• Tyrosine Transaminase is a PLP dependent.

11. Step 3
• p-hydroxyphenylpyruvate  homogentisate
by “p-Hydroxyphenylpyruvate hydroxylase”

12. Step 4
• Homogentisate  4-maleylacetoacetate by
“Homogentisate oxidase”
– Homogentisate oxidase cleaves the benzene ring– Homogentisate oxidase cleaves the benzene ring
of homogentisate.

13. Step 5
• Isomerization reaction.
• Maleylacetoacetate  4-fumaryl acetoacetate
by “maleylacetoacetate isomerase”by “maleylacetoacetate isomerase”

14. Step 6
• Hydrolysis of 4-fumaryl acetoacetate.
• 4-Fumaryl acetoacetate  Fumarate and
Acetoacetate by fumaryl acetoacetate hydrolase.
Fumarate:Fumarate:
– Intermediate of citric acid cycle.
– Precursor for gluconeogenesis.
Acetoacetate:
– Ketone body for fat synthesis.

16. Pathway continued from previous page

17. Disorders Of Tyrosine Metabolism
Enzyme defects in phenylalanine/ tyrosine
degradation leads metabolic disorders. Few
are discussed below:
– Phenyketonuria
– Albinism
– Alkaptonuria
– Tyrosinemia

18. Phenylketonuria (PKU)
• Phenylketonuria (PKU) is the most common metabolic
disorder in amino acid metabolism.
• Due to deficiency of enzyme: Phenylalanine
Hydroxylase, caused by an autosomal recessive gene.Hydroxylase, caused by an autosomal recessive gene.
• Due to a defect in dihydrobiopterin reductase, the
synthesis of tetrahydrobiopterin is impaired, which is
required for the action of phenylalanine hydroxylase.
• In PKU: Phenylalanine is not converted to Tyrosine.

20. Phenylalanine metabolism in PKU:
Phenylketonuria: Causes the accumulation of
phenylalanine in tissues and blood, and results in its
increased excretion in urine.
Due to error, phenylalanine follows alternate pathways
resulting in the excessive production of
Due to error, phenylalanine follows alternate pathways
resulting in the excessive production of
phenylpyruvate, phenylacetate, phenyllactate and
phenylglutamine.
All these metabolites are excreted in urine in high
concentration in PKU.

22. Clinical manifestations of PKU:
• Effects on central nervous system:
– Mental retardation
– Failure to walk or talk
– Failure of growth
– Seizures and tremor
– If untreated, the patients show very low IQ.– If untreated, the patients show very low IQ.
• Effect on pigmentation:
– Melanin is the pigment synthesized from tyrosine by tyrosinase.
Accumulation of phenylalanine competitively inhibits tyrosinase and
impairs melanin formation.
• Defect in myelin formation:
– Accumulation of phenylalanine competitively inhibits tyrosinase and
impairs melanin formation.

23. • Diagnosis of PKU : This is usually carried out by
Guthrie test.
• Treatment of PKU: The maintenance of plasma
phenylalanine concentration within the normal
range is a challenging task in the treatment of
PKU.PKU.
• Since the amino acid tyrosine cannot be
synthesized in PKU patients, it becomes essential
and should be provided in the diet in sufficient
quantity.

24. Albinism
Albinism is an inborn error, due to the lack of synthesis of the pigment
melanin.
It is an autosomal recessive disorder.
The melanin synthesis can be influenced by a variety of factors:
1. Deficiency or lack of the enzyme tyrosinase.
2. Decrease in melanosomes of melanocytes.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.
The most common cause of albinism is a defect in tyrosinase.

25. Clinical manifestations:
• Lack of melanin in albinos makes them
sensitive to sunlight.
• Increased susceptibility to skin cancer.• Increased susceptibility to skin cancer.
• Photophobia is associated with lack of
pigment in the eyes.

26. Alkaptonuria (Black urine disease)
• Homogentisate Oxidase is the defective enzyme in
in alkaptonuria in tyrosine metabolism.
• Homogentisate accumulates in tissues & blood,
and is excreted into urine.
Homogentisate accumulates in tissues & blood,
and is excreted into urine.
– Homogentisate gets oxidized to quinones, which
polymerize to give black or brown colour.
– That’s why, the urine of alkaptonuric patients resembles
coke in colour.

27. • Biochemical manifestations: Homogentisate gets oxidized by
polyphenol oxidase to benzoquinone acetate which
undergoes polymerization to produce a pigment called
alkapton.
• Alkapton deposits in connective tissue, bones and various
organs (nose, ear etc.) resulting in a condition known asorgans (nose, ear etc.) resulting in a condition known as
ochronosis.

28. Diagnosis: Urine gives positive test with ferric
chloride and silver nitrate.
Treatment: Consumption of protein diet with
low phenylalanine content is recommended.low phenylalanine content is recommended.

29. Tyrosinosis or tyrosinemia type I
Due to deficiency of enzymes: fumarylacetoacetate
hydroxylase and/or maleylacetoacetate isomerase.
Tyrosinosis: Rare but Serious disorder.
It causes liver failure, rickets, renal tubular dysfunction and
polyneuropathy. Tyrosine and many other amino acids arepolyneuropathy. Tyrosine 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.
Treatment: Diets low in tyrosine, phenylalanine and
methionine are recommended.

30. Tyrosinemia type II
Also known as Richner- Hanhart syndrome, is due to a defect in
the enzyme tyrosine transaminase.
This result in a blockade of the pathway of tyrosine. And it leads to
Accumulation and excretion of tyrosine and its metabolites are
observed.
Tyrosinemia type II is characterized by skin (dermatitis) and eyeTyrosinemia type II is characterized by skin (dermatitis) and eye
lesions and, rarely, mental retardation. A disturbed self-
coordination is seen in these patients.
Neonatal tyrosinemia The absence of the enzyme p-
hydroxyphenylpyruvate dioxygenase causes neonatal
tyrosinemia. This is mostly a temporary condition and usually
responds to ascorbic acid.