3. Phenylalanine, tyrosine and tryptophan are the
aromatic amino acids.
Metabolism of these AAs deserves special mention,
No. of biologically important compounds are produced from
them.
Deficiency of enzymes in the metabolic pathways of these
AAs results in no. of inborn errors of clinical importance.
Phenylalanine and tryptophan are nutritionally
essential amino acids but tyrosine is not as it can
be synthesized from phenylalanine.
All are both glucogenic as well as ketogenic.
4.
5. aromatic & essential amino acid
Both Glucogenic & Ketogenic
Phenylalanine is converted to tyrosine.
Referred to as 'sparing action' of tyrosine on
phenylalanine.
P h e n y l a l a n i n e
Phenylalanine
– CH2-CH-COOH
NH2
_
6. Overview of P h e n y l a l a n i n e a n d t y r o s i n e
metabolism
Phenylalanine
tyrosine
Protein
Glucose
Fat
Thyroid
hormones,
(T3, T4)
Norepinephrine,
epinephrine
(adrenal medulla)
Dopamine (CNS)
Melanin pigment
(skin, hair, eye)
10. Degradation of
Phenylalanine To tyrosine
Phenylalanine
Tyrosine
Phenylalanine
hydroxylase
– CH2-CH-COOH
NH2
_
HO – – CH2-CH-COOH
NH2
_ Tyrosine
transaminase
Glutamate
α-ketoglutarate
p-hydroxyphenylpyruvate
HO – – CH2-C-COOH
O
=
11. Degradation of
Phenylalanine To tyrosine
p-hydroxyphenylpyruvate
HO – – CH2-C-COOH
O
=
p-HPP
dioxygenase
Homogentisate
– CH2-COOH
Dehydroascorbate
H2O, CO2
Ascorbate
Homogentisate
oxidase
4-Maleylacetoacetate
– CH2-COOHC
CO-
O
O
=
O
O2
12. Degradation of
Phenylalanine To tyrosine
4-Maleylacetoacetate
H-C-C-CH2-C-CH2-COOH
H-C-COOH
=
=
=
O O
Maleylacetoacetate
isomerase
Glutathione
4-Fumaylacetoacetate
H-C-C-CH2-C-CH2-COOH
HOOC-C-H
=
=
=
O O
13. Degradation of
Phenylalanine To tyrosine
4-Fumarylacetoacetate
H-C-C-CH2-C-CH2-COOH
HOOC-C-H
=
=
=
O O
Fumarate
H-C-COOH
HOOC-C-H
=
Acetoacetate
CH3-C-CH2-COOH
=
O
Glucose
Acetyl CoA
Lipids
Fumarylacetoacetate
hydrolase
16. Biologically Important Compounds Derived
from Tyrosine
Tyrosine serves as a precursor for…
Catecholamines
Dopamine
Norepinephrine
Epinephrine
Thyroid hormones
T4
T3
Melanin pigment
17. synthesis of
Catecholamines
Epinephrine (adrenaline), norepinephrine
(noradrenaline) and dopamine are collectively called
catecholamines.
They are synthesized from tyrosine.
Epinephrine & norepinephrine are produced by
adrenal medulla & serve as hormones. Whereas,
dopamine and norepinephrine produced in the CNS
& postganglionic sympathetic nerves act as
neurotransmitter.
In Parkinson’s disease, dopamine levels in the CNS
are decreased because of a deficiency of cells that
produce dopamine.
19. Functions of catecholamines
Norepinephrine and epinephrine regulate
carbohydrate and lipid metabolisms.
They stimulate the degradation of triacylglycerol and
glycogen.
They cause an increase in the blood pressure.
Dopamine and norepinephrine serve as
neurotransmitters in the brain & autonomous
nervous system.
20. Dopamine and Parkinson’s disease
Parkinson’s disease is a common disorder in
many elderly people, with about 1% of the
population above 60 years being affected.
It is characterized by…
Muscular rigidity,
Tremors,
Expressionless face,
Lethargy,
Involuntary movements etc.
21. Dopamine and Parkinson’s disease
Biochemical basis :
The exact biochemical cause of this disorder has
not been identified.
It is, however, linked with a production of
dopamine.
The disease is due to degeneration of certain
parts of the brain (substantia nigra and locus
coeruleus), leading to the impairment in the
synthesis of dopamine.
22. Dopamine and Parkinson’s disease
Treatment :
Dopamine cannot enter the brain, hence its
administration is of no use.
DOPA (levodopa or L-dopa) is used in the treatment of
Parkinson’s disease.
In the brain, DOPA is converted to dopamine which
alleviates the symptoms of PD.
Unfortunately, dopamine synthesis occurs in various
other tissues & results in side-effects such as nausea,
vomiting, hypretension etc.
Administration of DOPA analogs—that inhibit dopa
decarboxylase (in various tissues) but not enter brain
(due to BBB)—are found to be effective.
Carbidopa & γ-methyl-dopa (dopa analogs) are
administered along with dopa for the treatment of
Parkinson’s disease.
25. Melanin —the colour pigment:
The skin colour of the individual is determined by the
relative conc. of black and red melanins.
This, in turn, is dependent on many factors, both
genetic and environmental.
These include the activity of tyrosinase, the density
of melanocytes, availability of tyrosine etc.
Albinism is an inborn error with generalized lack of
melanin synthesis.