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