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 5^th 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