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CURS 1
Hypothyroidism
Hyperthyroidism
Addison disease
Cushing disease
Acromegaly
Pheochromocytoma
(tumorof themedullaof the adrenal glands)
Catecholamines
(Adrenalin, Noradrenalin, Dopamine)
Catecholamines
Biologically-active water-soluble amines derived
from tyrosine that serve as neurotransmitters in the
CNS and as hormones in circulation in response to
psychological stress (fight or flight response) or
hypoglycemia:
Epinephrine (adrenaline)
Norepinephrine (noradrenlaine)
Dopamine
All three and are produced in chromaffin cells of
the adrenal medula of the sympathetic nervous
system and and post-ganglionic fibers of the
sympathetic division of the autonomic nervous
system.
Dopamine also acts as a neurotransmitter in the
CNS and is synthesized by neuronal cell bodies of
the substantia nigra and ventral tegmental area in
the midbrain (as well as serotonin)
Biosynthesis of
Catecholamines
Synthesis of Catecholamines
Degradation of
Catecholamines
Dopa decarboxylase
1. Cofactor: pyridoxine; low Km but high Vmax
2. Also decarboxylate 5-HTP and other aromatic a.a.:
aromatic amino acid decarboxylase (AAAD)
3. Inhibitor: -methyldopa
Dopamine -hydroxylase
1. Cofactor: ascorbate; substrate: dopamine
2. Inhibitor: diethyldithiocarbamate (copper chelator)
3. DBH is a tetrameric glycoprotein (77kDa and 73kDa)
4. Store in the synaptic vesicle and releasable
Phenylethanolamine N-methyltransferase
(PNMT) regulated by
Substrate: S-adenosylmethionine;
corticosteroids
Metabolism of dopamine
Major acidic
metabolites:
A. 3,4-dihydroxy
phenylacetic acid
(DOPAC)
B. Homovallic acid
Inactivation of Norepinephrine
Catechol-O-methyltransferase
1. (COMT)
Enzyme can metabolize both intra- or extracellularly
2. Requires Mg2+ and substrate of S-adenosylmethionine
1.
Features of Adrenergic
receptors
Both NE and epinephrine bind to and receptors
propanolol
yohimbine
Dynamics of catecholamine
receptors
agonist
antagonist
catecholamine receptor