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