Catecholamines - biosynthesis, biodegradation

Catecholamines are compounds that function as neurotransmitters and hormones in various physiological processes. These chemical messengers include dopamine, noradrenaline, and adrenaline, which are derived from the amino acid tyrosine. Dopamine is primarily synthesized in the brain, particularly in areas such as the substantia nigra and ventral tegmental area, where it functions mainly as a neurotransmitter. Noradrenalin and adrenalin are secreted by the adrenal medulla and sympathetic nerve endings and act as hormones and neurotransmitters influencing vital bodily functions.

Catecholamines are crucial for various physiological processes, including stress responses, cardiovascular function, and mood regulation. Dysregulation of catecholamine production or signaling can disrupt these essential processes, contributing to disorders such as hypertension, heart failure, anxiety, and neurodegenerative diseases.

Biosynthesis of catecholamines ===

The biosynthesis of catecholamines starts with the amino acid tyrosine, which is hydroxylated to L-DOPA by tyrosine hydroxylase. L-DOPA is then decarboxylated to dopamine. In sympathetic nerve endings, dopamine is converted into noradrenalin by dopamine β-hydroxylase. In the adrenal medulla, noradrenalin is methylated to form adrenalin through phenylethanolamine N-methyltransferase. These processes are crucial for the functioning of the central nervous system, as well as stress and cardiovascular responses.

Tyrosine → L-DOPA Tyrosine hydroxylase converts tyrosine into L-DOPA.

L-DOPA → Dopamine L-DOPA is decarboxylated into dopamine by aromatic L-amino acid decarboxylase.

Dopamine → Noradrenalin In the synaptic vesicles, dopamine is converted into norepinephrine by dopamine β-hydroxylase.

Noradrenalin → Adrenalin In the adrenal medulla, noradrenalin is methylated to adrenalin by phenylethanolamine N-methyltransferase.

biodegradation of catecholamines

• MAO (Monoamine Oxidase) breaks down catecholamines like dopamine, noradrenalin, and adrenalin into their aldehyde intermediates: DOPAL (dopamine) and DOPEGAL (noradrenalin/adrenalin).
• Aldehyde dehydrogenase (AD) or aldehyde reductase (AR) metabolize DOPAL and DOPEGAL further into compounds like DOPAC, DOPET, DHMA, and DHPG.
• COMT (Catechol-O-Methyltransferase) methylates DOPAC into HVA (homovanillic acid) and DHPA into MHPG.
• For noradrenalin and adrenalin, the final metabolite is VMA (Vanillylmandelic acid).

MAO (Monoamine Oxidase) Breaks down:

Dopamine → DOPAL Noradrenalin/adrenalin → DOPEGAL Aldehyde dehydrogenase (AD) or aldehyde reductase (AR) Metabolizes intermediates into:

DOPAL → DOPAC DOPEGAL → DOPET, DHMA, DHPG COMT (Catechol-O-Methyltransferase) Methylates:

DOPAC → HVA DHPA → MHPG Final Product

Noradrenalin/adrenalin → VMA (Vanillylmandelic acid)