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Tyrosine

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Tyrosine is a non essential Amino Acid synthesized from hydroxylation of phenylalanine by the phenylalanine hydroxylase

phenylalanine

Tyrosine

Metabolism of Tyrosine wad divided into 2 parts:

1. Transamination Pathway.

2. Synthesis of specialized products.
A- Thyroid Hormones T3. T4.
B- Adrenalin & nor adrenalin.
C-Melanin pigment of the skin
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Transamination of Tyrosine

oxidase
Schematic presentation of Tyrosine Metabolism
parahydroxyphenylpyruvate hydroxylase
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The end result of tyrosine metabolism are1.Fumarate …………. Citric Acid cycle2.Acetoacetate& Acetate……………..Fatty Acid SynthesisTyrosine is both glucogenic & KetogenicFumarate GlucogenicAcetoacetate Ketogenic A
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Inborn Error diseases of Tyrosine (Metabolic disorders)

Type 2 Tyrosinemia
Neonatal Tyrosinemia
Alkapotoneuria
Type 1 Tyrosinemia

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Type 2 Tyrosinemia

#Deficiency of tyrosine transaminase.
# mild to severe keratitis.erosive lesion of the palm,,
# Skin lesions, hyperkeratosis of the palm and the hand.
#Mental retardation.
# High level of tyrosine in the blood.
# harmful untreatable disease.
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Neonatal Tyrosinemia

#Deficiency of parahydroxyphenyl pyruvate hydroxylase.

# Accumulation of parahydroxyphenyl pyruvic acid (Toxic).

# Hepatosplenomegally.

#Harmful untreatable Death before the age of 6 months
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Alkaptonuria

# Autosomal recessive.
#Deficiency of homogentisic acid oxidase.
#Increase homogentisic acid in blood and urine.
#Homogentisic acid on standing become black pigment. .(Alkapotonuria)
#It may be precipitate in the cartilage specially in the ear.
#Harmless.
#Diagnosis: Black color urine.
#Ferric chloride test is positive.
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Type1 Tyrosinemia (Tyrosinosis)

# Acute form lead to vomiting&diarrhoea.
#Failure to thrive.
#Deficiency of Fumaryl acetate hydroxylase.
#Mostly die before age of 6-8 months (Acute form).
#Death due to liver failure.
#Chronic form similar but milder ,death usually before age of 10 Years.
#Example of harmful untreatable diseases.
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Metabolism of tyrosine in melanocyte(skin)

Schematic presentation of Tyrosine metabolism in the skin
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Metabolism of Tyrosine in the melanocyte(Skin)

1.Hydroxylation of tyrosine by tyrosinase enzyme to form dihydroxyphenylalanine(L-Dopa).

2. Dihydroxyphenylalanine is converted to Dopaquinone.

3.Dopaquinone is converted to melanin pigment.

4. L-Dopa is decarboxylated in the brain to form Dopamine.( epinephrine and nor epinephrine.)

5.Dopamine is deficient in brain patient with parkinsonism.

6.Minor pathway is that tyrosine is decarboxylated to form tyramine a vasopressor agent.

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Inborn Error (Metabolic disease)of Tyrosine in the skin.

Albinism.
# Deficiency of tyrosinase enzyme of melanocytes.

#Failure of melanocyte to form melanin pigments.
#Whitish skin, Whitish eye lashes, whitish hair

#Intolerance to sunlight.

#Harmless condition.
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Parkinson disease is linked with decrease production of dopamine .The disease is due to degeneration of certain part of the brain leading to impairment synthesis of dopamine.

Treatment: dopamine can not enter the brain hence its administration is of no use.

L- dopa or levodopa is used in the treatment of Parkinson . In the brain DOPA is decarboxylated to dopamine which alleviates the symptoms but dopamine synthesis occurs in various tissue causing side effect, such as nausea, vomiting hypertension

Sinemet contain L=Dopa 250mg and carbidopa 25mg act as peripheral decarboxylase inhibitor to prevent decarboxylation in various tissue and decrease the side effect
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Tissue Proteins

Diet
Phenylalanine
Tyrosine
DOPA
Melanin
DA
(dopamine)
NE
(norepinephrine)
p-hydroxy-
phenlypyruvate
homogentisic
acid
thyroxine
phenyl-
pyruvic acid
PAH
The main metabolic pathways of phenylalanine and tyrosine in the human
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Tissue Proteins

Diet
Phenylalanine
Tyrosine
DOPA
Melanin
DA
(dopamine)
NE
(norepinephrine)
phenyl-
pyruvic acid
PKU
Albinism
p-hydroxy-
phenlypyruvate
homogentisic
acid
thyroxine
Alkaptonuria
goitrous
cretinism
Tyrosinosis
Schematic presentation of main inborn error of metabolism of Tyrosine
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رفعت المحاضرة من قبل: Deaa Al-deen El-taee
المشاهدات: لقد قام عضوان و 42 زائراً بقراءة هذه المحاضرة






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