Tyrosine hydroxylase or
tyrosine 3-monooxygenase is the
enzyme responsible for catalyzing the conversion of the
amino acid L-tyrosine to
dihydroxyphenylalanine (DOPA). It does so using
tetrahydrobiopterin as a
coenzyme. DOPA is a precursor for
dopamine, which, in turn, is a precursor for
norepinephrine (noradrenaline) and
epinephrine (adrenaline). In humans, tyrosine hydroxylase is encoded by the
TH gene.
Reaction
The enzyme, an
oxygenase, is found in the
cytosol of all cells containing
catecholamines. This initial reaction is the
rate limiting step in the production of catecholamines.
The enzyme is highly specific, not accepting
indole derivatives - which is unusual as many other enzymes involved in the production of catecholamines do.
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Clinical significance
Tyrosine hydroxylase can be inhibited by the drug α-methyl-para-tyrosine (
Metirosine). This inhibition can lead to a depletion of dopamine and norepinepherine in the brain due to the lack of the precursor L-Dopa (L-3,4-dyhydroxyphenylalanine) which is synthesized by tyrosine hydroxylase. This drug is rarely used and can cause depression, but it is useful in treating
pheochromocytoma and also resistant
hypertension.
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Tyrosine hydroxylase is an autoantigen in
Autoimmune Polyendocrine Syndrome ......
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