Biosynthesis of dopamine, adrenaline, nor- adrenaline, serotonin and melatonin

Biosynthesis of
dopamine, adrenaline, nor- adrenaline, serotonin and melatonin

Objective

At the end of this lecture, student will be
able to

       Discuss
the biosynthesis of dopamine, adrenaline, nor- adrenaline, serotonin and
melatonin

Biosynthesis of catecholamines

       Tyrosine is the precursor for the synthesis
of
catecholamines, namely dopamine, noradrenaline and adrenaline

       Conversion
of tyrosine to catecholamines occurs in adrenal medulla and CNS

       Tyrosine is hydroxylated to
3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase, this enzyme
catalyses the rate limiting reaction and requires tetrahydrobiopterin as
coenzyme

       In contrast to this enzyme,
tyrosinase present in melanocytes converts tyrosine to DOPA. Hence, two
different enzyme systems exist to convert tyrosine to DOPA

       DOPA undergoes PLP-dependent
decarboxylation to give dopamine which, in turn, is hydroxylated to produce
norepinephrine

       Methylation of norepinephrine by
S-adenosylmethionine gives epinephrine

       The difference between epinephrine
and norepinephrine is only a methyl group

       Norepinephrine is produced in
certain areas of the brain while dopamine is predominantly synthesized in
substantia nigra and coeruleus of brain

Functions of Catecholamines

       Norepinephrine and epinephrine
regulate carbohydrate and lipid metabolism

       They stimulate the degradation of
triacylglycerol and glycogen

       They cause an increase in the blood
pressure

       Dopamine and norepinephrine serve as
neurotransmitters in brain and autonomous nervous system

Synthesis of serotonin

       In mammals, the largest amount of
serotonin is synthesized in the intestinal cells

       Tryptophan is first hydroxylated at
5th carbon by tryptophan hydroxylase, requires tetrahydrobiopterin
as a cofactor

       5-Hydroxytryptophan is
decarboxylated by aromatic amino acid decarboxylase (PLP dependent) to give
serotonin

Functions of serotonin

       Serotonin is a neurotransmitter and
performs a variety of functions

1.
Serotonin is a powerful vasoconstrictor and results in smooth muscle
contraction in
bronchioles
and arterioles

2. lt is
closely involved in the regulation of cerebral activity (excitation)

3.
Serotonin controls the behavioural patterns, sleep, blood pressure and body
temperature

4.
Serotonin evokes the release of peptide hormones from gastrointestinal tract

5. lt is
also necessary for the motility of GIT (peristalsis)

Biosynthesis of melatonin

       Tryptophan to Melatonin

Functions of melatonin

       It is involved in circadian rhythm
of the body

       It plays significant role in sleep
and wake process

       It inhibits the production of
melanocyte stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH)

       It also performs neurotransmitter
function

Summary

       Phenylalanine & tyrosine are
structurally related aromatic amino acids

       Tyrosine is a precursor for the
synthesis of epinephrine, nor-epinephrine, dopamine, thyroid hormones and
pigment melanin etc

       Tryptophan is a precursor for the
synthesis of serotonin and melatonin

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