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Is there someone on the list who either is a biochemist or knows one who
might be interested in answering the following question about the regulation
of dopamine synthesis.

I looked in the book 'Biochemistry' by Stryer and in 'Biochemistry' by Voet
and Voet and got the following information, which is the starting point for
my question about dopamine.

The rate limiting step in the synthesis of the neurotransmitter, dopamine,
from the amino acid, tyrosine, in the brain is:

tyrosine + O2 + tetrahydrobiopterin

---> dopa + H2O + quinonoid dihydrobiopterin.

This reaction is catalyzed by tyrosine hydroxylase, a monooxidase like
phenylalanine hydroxylase.  Dopa (i.e., Levodopa) is an abbreviation for
3,4-dihydroxyphenylalanine.

Tetrahydrobiopterin, the cofactor that activates molecular oxygen in this
reaction, is regenerated by the reaction:

quinonoid dihydrobiopterin + NADH + H+

---> tetrahydrobiopterin + NAD+ + H2O,

which is catalyzed by dihydropteridine reductase.

The overall net reaction catalyzed by tyrosine hydroxylase and
dihydropteridine reductase is

tyrosine + O2 + NADH + H+ ---> dopa + NAD+ + H2O.

The next step is:  dopa ---> dopamine,  which is catalyzed by
dopa decarboxylase.

Dopamine is degraded in the reaction:

dopamine ---> 3-o-methyldopamine,

which is catalyzed by catechol-o-methyltransferase (COMT),
and in the reaction:

dopamine ---> 3,4-dihydroxyphenylethylaldehyde,

which is catalyzed by monoamineoxidase-B (MAO-B).

My question is:  How is the level of dopamine regulated?
Does dopamine inhibit tyrosine hydroxylase  or does it inhibit the
expression of the enzyme?  What is the specific mechanism for
the inhibition reaction?  That is, what are the specific reactions
that accomplish the regulation?

Baldwin Robertson ...           [log in to unmask]