It is aromatic & essential amino acid.
Both Glucogenic & Ketogenic.
Phenylalanine is converted to tyrosine.
Referred to as 'sparing action' of tyrosine
on phenylalanine.
Predominant metabolism of phenylalanine
occurs through tyrosine.
Tyrosine is incorporated into proteins & is
involved in the synthesis of variety of
biologically important compounds-
epinephrine, norepinephrine, dopamine,
thyroid hormones & the pigment melanin.
Degradation of phenylalanine mostly occurs
through tyrosine.
Phenylalanine is hydroxylated at para-
position by phenylalanine hydroxylase to
produce tyrosine.
This reaction is irreversible, & requires
specific coenzyme biopterin, which is
structurally related to folate.
Active form of biopterin is tetrahydrobiopterin.
Tetrahydrobiopterin is oxidized to
dihydrobiopterin.
Tetrahydrobiopterin is then regenerated by an
NADPH-dependent dihydrobiopterin
reductase.
Phenylalanine hydroxylase is present in liver.
In the conversion of phenylalanine to
tyrosine, the reaction involves incorporation
of one atom of molecular oxygen into para-
position of phenylalanine while the other
atom O2 is reduced to form water.
Tetrahydrobiopterin supplies reducing
equivalents.
Phenylalanine is converted to tyrosine, a
single pathway is responsible for the
degradation of both these amino acids.
Occurs mostly in liver.
Tyrosine first undergoes transamination to P-
hydroxyphenyl pyruvate, catalyzed by
tyrosine transaminase (PLP dependent)
p-hydroxy phenylpyruvate hydroxylase (or
dioxygenase) is a copper-containing
enzyme.
It catalyzes oxidative decarboxylation as
well as hydroxylation of the phenyl ring of
p-hydroxy phenyl pyruvate to produce
homogentisate.
This reaction involves a shift in hydroxyl
group from para position to meta position &
incorporates a new hydroxyl group at para
position to give 2,5-dihydroxyphenylacetic
acid or homogentisic acid.
This step requires ascorbic acid.
Homogentisate oxidase (iron metallo-
protein) cleaves the benzene ring of
homogentisate to form 4-maleylacetoacetate.
Molecular oxygen is required for this
reaction to break the aromatic ring.
4-Maleylacetoacetate undergoes
isomerization to form 4-fumaryl acetoacetate.
Catalyzed by maleylacetoacetate isomerase.
Fumaryl acetoacetase (fumaryl acetoacetate
hydrolase) brings about the hydrolysis of
fumaryl acetoacetate to liberate fumarate &
acetoacetate.
Fumarate is an intermediate in citric acid
cycle & can serve as precursor for
gluconeogenesis.
Acetoacetate is a ketone body from which
fat can be synthesized.
Phenylalanine & tyrosine are both
glucogenic & ketogenic amino acids.
Melanin is a pigment of skin, hair & eye.
The synthesis of melanin occurs in
melanosomes present in melanocytes, the
pigment producing cells.
Tyrosine is precursor for melanin & only one
enzyme, namely tyrosinase (a copper
containing oxygenase), is involved in its
formation.
Tyrosinase hydroxylates tyrosine to form 3,4-
dihydroxy-phenylalanine (DOPA).
DOPA can act as a cofactor for tyrosinase.
DOPA is converted to dopaquinone by
tyrosinase.
Dopaquinone in subsequent couple of
reactions occur spontaneously, forming
leucodopachrome followed by 5,6-dihydroxy
indole.
The oxidation of 5,6-dihydroxyindole to indole
5,6-quinone is catalyzed by tyrosinase.
DOPA serves as a cofactor.
This reaction, inhibited by tyrosine regulates
the synthesis of melanin.
Melanochromes are formed from indole
quinone, which on polymerization are
converted to black melanin.
Another pathway:
Cysteine condenses with dopaquinone & in the
next series of reactions results the synthesis of
red melanins.
Melanin-the color pigment:
The skin color of the individual is determined
by the relative concentrations of black & red
melanins.
This, in turn, is dependent on many factors,
both genetic & environmental.
These include the activity of tyrosinase, the
density of melanocytes, availability of tyrosine
etc.
The presence of moles on the body represents
a localized severe hyperpigmentation due to
hyperactivity of melanocytes.
Localized absence or degeneration of
melanocytes results in white patches on the
skin commonly known as leucoderma.
Albinism is an inborn error with generalized
lack of melanin synthesis.
Thyroid hormones - Thyroxine
(tetraiodothyronine) & triiodithyronine - are
synthesized from the tyrosine residues of
the protein thyroglobulin & activated iodine.
Iodination of tyrosine ring occurs to produce
mono & diiodotyrosine from which
triiodothyronine (T3) & thyroxine (T4) are
synthesized.
The protein thyroglobulin undergoes
proteolytic breakdown to release the free
hormones - T3 & T4.
Catecholamines are derived from tyrosine.
The name catechol refers to the
dihydroxylated phenyl ring (catechol nucleus).
The amine derivatives of catechol are called
catecholamines.
Tyrosine is the precursor for the synthesis of
catecholamines, namely dopamine,
norepinephrine (noradrinaline) &
epinephrine (adrinaline)
Conversion of tyrosine to catecholamines
occurs in adrenal medulla & central nervous
system.
Tyrosine hydroxylase:
Tyrosine is hydroxylated to 3,4-
dihydroxyphenylalanine (DOPA) by tyrosine
hydroxylase.
It is a rate limiting enzyme & requires
tetrahydrobiopterin as coenzyme.
In contrast to this enzyme, tyrosinase present
in melanocytes converts tyrosine to DOPA.
Two different enzyme systems exist to convert
tyrosine to DOPA.
DOPA-decarboxylase:
DOPA undergoes PLP-dependent
decarboxylation to give dopamine.
Dopamine is a catecholamine.
Dopamine is an inhibitor of prolactin secretion
Dopamine is neurotransmitter in substantia
nigra, extrapyramidal tract, & striatal tract.
In Parkinsonism, the dopamine content in
brain is reduced.
As dopamine will not enter into the brain
cells, the precursor, L-DOPA is used as a drug
in Parkinsonism.
Alpha methyl DOPA will inhibit DOPA
decarboxylase & prevent production of
epinephrine; so it is an antihypertensive
drug.
Nor epinephrine:
Dopamine is further hydroxylated to nor-
epinephrine or noradrenaline
The term “nor” denotes that the molecule
does not contain the "R" or methyl group.
Methylation of norepinephrine by S-
adenosylmethionine gives epinephrine.
Epinephrine:
Nor-epinephrine is methylated by the
enzyme N-methyl transferase to epinephrine
or adrenaline.
S-adenosyl methionine (SAM) is the methyl
donor.
It is mainly produced by adrenal medulla &
adrenergic nerve endings.
The difference between epinephrine &
norepinephrine is only a methyl group.
In adrenal medulla, synthesis of the
hormones, norepinephrine & epinephrine is
prominent.
Norepinephrine is produced in certain areas
of brain while dopamine is predominantly
synthesized in substantia nigra.
They cause the increase in blood pressure.
Adrenaline also increases the rate & force of
myocardial contraction.
Adrenaline is anti-insulin in nature, it
increases glycogenolysis & stimulates
lipolysis.
Serve as neurotransmitters in the brain ANS.
The half-life of epinephrine is 2-5 minutes.
Epinephrine is catabolized in tissues, by
catechol-O-methyl transferase (COMT) to
metanephrine.
It is then acted upon by mono amine oxidase
(MAO).
MAO will oxidatively deaminate
metanephrine.
The major end product is 3-hydroxy-4-
methoxy mandelic acid or vanillyl mandelic
acid (VMA).
Homovanillic acid (HVA) in Urine:
It is also called methoxy hydroxy phenyl
acetic acid.
HVA is the main urinary metabolite of DOPA
& dopamine.
Textbook of Biochemistry-u Satyanarayana
Textbook of Biochemistry-DM Vasudevan