Phenylalanine and Tyrosine

Metabolism

Dr. Mohammad Akram

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 Phenylalanine
 Phenylalanine is an essential amino acid
(building block for proteins in the body). It
is essential to human health but cannot be
manufactured by the body. For this
reason, phenylalanine must be obtained
from food. The body converts
phenylalanine into tyrosine, another amino
acid essential for making proteins, brain
chemicals including dopamine and
norepinephrine, and thyroid hormones.
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 Phenylalanine and Tyrosine
Catabolism

Phenylalanine normally has only two fates:

incorporation into polypeptide chains, and
production of tyrosine via the
tetrahydrobiopterin-requiring
phenylalanine hydroxylase.

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 Pathway
From tyrosine, there are further
connections to the biosynthesis of
catecholamines, melanin, hormones, etc.
Usually, dietary intake of Phe and Tyr, and
the body's demand for Phe and Tyr, are
fairly closely balanced. However, when
there is too much phenylalanine in the
body's pool of amino acids, it must be
eliminated, either by excretion or by
biochemical reaction
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 PKU
In 'classic PKU', the enzyme that breaks
down phenylalanine, phenylalanine
hydroxylase, happens in the liver cells, is
completely or nearly completely deficient.
This enzyme normally converts
phenylalanine to another amino acid,
tyrosine. Without this enzyme,
phenylalanine and its' breakdown
chemicals from other enzyme routes,
accumulate in the blood and body tissues.
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 Cont.
 Tyrosine is converted in turn to 3-4-
dihydroxy phenylalanine (nick-named
DOPA) by another enzyme and DOPA
serves as a precursor for the hormones
adrenaline and noradrenaline and for the
black pigment, melanin.

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 Phenylalanine and Tyrosine
Catabolism

Therefore tyrosine is equally important for

protein biosynthesis as well as an
intermediate in the biosynthesis of several
physiologically important metabolites e.g.
dopamine, norepinephrine and
epinephrine.

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 Phenylalanine and Tyrosine
Catabolism
 As in phenylketonuria (deficiency of phenylalanine
hydroxylase, PAH), deficiency of tyrosine
aminotransferase (TAT) leads to hypertyrosinemia
and the urinary excretion of tyrosine and the catabolic
intermediates between phenylalanine and tyrosine.
The adverse neurological symptoms are similar for
PAH and TAT deficiencies. In addition,
hypertyrosinemia leads to painful corneal eruptions
and photophobia.

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 Main Route for Metabolism of
Phenylalanine
Phenylalanine is converted by the mono-
oxygenase, phenylalanine hydroxylase, to
tyrosine. This REDOX reaction requires
the cofactor tetrahydrobiopterin, which in
the course of the reaction is converted to
quinonoid dihydrobiopterin. The cofactor is
regenerated through the action of the
enzyme dihydropteridine reductase, which
in turn uses NADPH as a source of
reducing power.
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 Phenylalanine and Tyrosine
Catabolism
The first inborn error in metabolism ever
recognized, alkaptonuria, was demonstrated to be
the result of a defect in phenylalanine and tyrosine
catabolism. Alkaptonuria is caused by defective
homogentisic acid oxidase. Homogentisic acid
accumulation is relatively innocuous, causing urine
to darken on exposure to air, but no life-threatening
effects accompany the disease. The only untoward
consequence of alkaptonuria is ochronosis (bluish-
black discoloration of the tissues) and arthritis.

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 Phenylalanine metabolism

Reaction 1 is catalysed by
Phenylalanine hydroxylase and
Reaction 2 is catalysed by
phenylalanine transaminase.

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 Oxidation of Phenylalanine and
Biosynthesis of Tyrosine
If there is sufficient phenylalanine in the
diet, then humans usually have no
difficulty in synthesizing adequate
amounts of tyrosine from the dietary
phenylalanine. The reaction is complex:
This reaction is also the first reaction in the normal route of catabolism of phenylalanine.

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Oxidation of Phenylalanine and
Biosynthesis of Tyrosine cont.
The enzyme catalyzing the reaction is
phenylalanine hydroxylase (PAH), a
mixed-function mono-oxygenase that uses
molecular oxygen. This enzyme also uses
the cofactor tetrahydrobiopterin (BH4),
which is oxidized in the course of the
reaction to dihydrobiopterin (BH2). The
cofactor must be regenerated by a
separate system of enzymes for PAH
action to continue.
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Thank you

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