Overview
- biosynthesis of catecholamines is done in 3 (4) steps
TYROSINE
| tyrosine hydroxylase
DOPA
| DOPA decarboxylase
DOPAMINE
| dopamine beta-hydroxylase
NORADRENALINE
| phenylethanolamide N-methyltransferase (“PNMT”)
ADRENALINE
- , thus there are 3 (4) enzymes involved in catecholamine biosynthesis
ENZYME NAME
DESCRIPTION
TYROSINE HYDROXYLASE
- the rate-limiting step
- located in the cytoplasm of sympathetic postsynaptic neurons
DOPA DECARBOXYLASE
DOPAMINE BETA-HYDROXYLASE
PNMT
- general enzyme located in the cytoplasm of most cells
- catalyses decarboxylation of aromatic amino acids
- located in the synaptic vesicles of postsynaptic sympathetic nerve terminals
- located in the a-cells of the adrenal medulla
Relevant Drugs
- 3 types
DRUG NAME
DESCRIPTION
ALPHA-METHYLTYROSINE
METHYLDOPA
General information
- a tyrosine hydroxylase inhibitor
- inhibits tyrosine hydroxylase, thus causing inhibition of catecholamine synthesis
Clinical use
- treatment of pheochromocytoma (a catecholamine-
producing adrenal medullary tumor)
Side effects
- hypotension (due to vasodilation)
- drowsiness
General information
- a central DOPA decarboxylase inhibitor (may cross the blood-brain barrier)
- alternate substrate for DOPA decarboxylase , thus displacing DOPA from the active site of DOPA decarboxylase and following inhibition of catecholamine synthesis
- is converted by DOPA decarboxylase to methylnoradrenalin (a selective alpha-2 agonist, see 19)
Clinical use
- treatment of hypertension during pregnancy (by
inhibition of the sympathetic nuclei of the brainstem)
Side effects
- same as alpha-methyltyrosine (see above)
CARBIDOPA
- impotency
- hypersensitivity reactions
General information
- a peripheral DOPA decarboxylase inhibitor (may not
pass the blood-brain barrier)
Clinical use
- treatment of parkinson’s disease (by inhibition of the
use of DOPA for catecholamine synthesis in
peripheral neurons, thus freeing it for restorement of
the dopaminergic pathways of the brain
- biosynthesis of catecholamines is done in 3 (4) steps
TYROSINE
| tyrosine hydroxylase
DOPA
| DOPA decarboxylase
DOPAMINE
| dopamine beta-hydroxylase
NORADRENALINE
| phenylethanolamide N-methyltransferase (“PNMT”)
ADRENALINE
- , thus there are 3 (4) enzymes involved in catecholamine biosynthesis
ENZYME NAME
DESCRIPTION
TYROSINE HYDROXYLASE
- the rate-limiting step
- located in the cytoplasm of sympathetic postsynaptic neurons
DOPA DECARBOXYLASE
DOPAMINE BETA-HYDROXYLASE
PNMT
- general enzyme located in the cytoplasm of most cells
- catalyses decarboxylation of aromatic amino acids
- located in the synaptic vesicles of postsynaptic sympathetic nerve terminals
- located in the a-cells of the adrenal medulla
Relevant Drugs
- 3 types
DRUG NAME
DESCRIPTION
ALPHA-METHYLTYROSINE
METHYLDOPA
General information
- a tyrosine hydroxylase inhibitor
- inhibits tyrosine hydroxylase, thus causing inhibition of catecholamine synthesis
Clinical use
- treatment of pheochromocytoma (a catecholamine-
producing adrenal medullary tumor)
Side effects
- hypotension (due to vasodilation)
- drowsiness
General information
- a central DOPA decarboxylase inhibitor (may cross the blood-brain barrier)
- alternate substrate for DOPA decarboxylase , thus displacing DOPA from the active site of DOPA decarboxylase and following inhibition of catecholamine synthesis
- is converted by DOPA decarboxylase to methylnoradrenalin (a selective alpha-2 agonist, see 19)
Clinical use
- treatment of hypertension during pregnancy (by
inhibition of the sympathetic nuclei of the brainstem)
Side effects
- same as alpha-methyltyrosine (see above)
CARBIDOPA
- impotency
- hypersensitivity reactions
General information
- a peripheral DOPA decarboxylase inhibitor (may not
pass the blood-brain barrier)
Clinical use
- treatment of parkinson’s disease (by inhibition of the
use of DOPA for catecholamine synthesis in
peripheral neurons, thus freeing it for restorement of
the dopaminergic pathways of the brain
