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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