00:01
So phenylalanine is an
essential amino acid.
00:04
That means, of course, it
has to be in our diet.
00:06
It is also a precursor of
the amino acid tyrosine.
00:10
Now phenylalanine metabolism requires
the enzyme phenylalanine hydroxylase.
00:15
That catalyzes the formation
of tyrosine form phenylalanine
in the reaction that we can
see here on the right.
00:22
In this reaction, phenylalanine
is getting a hydroxyl group.
00:25
And this is a complicated
hydroxylation reaction
that involves tetrahydrobiopterin
and molecular oxygen.
00:32
The products of that reaction
being dihydrobiopterin and water,
plus the amino acid phenylalanine and
you can see the different between the
phenylalanine and the tyrosine is the
addition of that hydroxyl group.
00:44
A deficiency of this enzyme, phenylalanine
hydroxylase, is very, very important
because this enzyme when it's deficient
causes the disease known as phenylketonuria.
00:56
Fortunately, phenylketonuria
can be treated if it's
diagnosed early and it's
commonly diagnosed at birth.
01:02
If it's not diagnosed and not
recognized early enough,
then high levels of
phenylalanine in the diet
damage the brain and you get
sever neurological consequences.
01:12
Now fortunately, as I said, it's
treatable by reducing the amount of
phenylalanine that a person gets in
their diet, and this works fairly well.
01:19
But one of the complicating
factors is that the
artificial sweetener, Nutrasweet,
contains phenylalanine.
01:27
So a person who has phenylketonuria
should absolutely not consume Nutrasweet,
and that's why you see
the warning on cans of
soda, for example, that
contain Nutrasweet.
01:39
Tyrosine is an amino acid whose
essentialness or not essentialness
depends upon whether or not
phenylalanine is present.
01:46
If it's present in the diet,
then tyrosine is not essential
because tyrosine can be
made from phenylalanine.
01:52
Tyrosine is important as a
precursor of catecholamines.
01:56
So just as tyrosine was a product
of phenylalanine breakdown,
the catecholamines are a
product of tyrosine breakdown.
02:04
There are four important catecholamines
that are made from tyrosine:
L-DOPA, L-dopamine,
norepinephrine, and epinephrine.
02:12
These molecules are
important hormones
and neurotransmitters that
function in our brain.
02:19
Tyrosine also is important because it is a
source of electrons to reduce chlorophyll
in photosystem II during the
process of photosynthesis.
02:28
Tyrosine forms the radical that's essential
for the function of ribonucleotide
reductase which I will discuss in the
lectures on nucleotide metabolism.
02:39
Now tyrosine's synthesis of the four
catecholamines is shown in this slide.
02:44
As I said, this is actually the breakdown
of tyrosine that produces this.
02:48
We see the first product being made from
tyrosine here using tyrosine hydroxylase
and again, tetrahydrobiopterin
and molecular oxygen,
producing dihydrobiopterin and water
and this compound called L-DOPA.
03:02
We can see that L-DOPA
defers from tyrosine
by the addition of a
single hydroxyl group.
03:08
L-DOPA is converted into L-dopamine by
the enzyme aromatic acid decarboxylase,
and as its name suggests, this
involves lost of a carboxyl group
which is occurring on the
left portion of the molecule
and that's where we see the difference
between the L-dopamine and L-DOPA.
03:26
L-dopamine itself then can be converted
into norepinephrine by a reaction
involving vitamin C, this is where vitamin
C is important, molecular oxygen.
03:36
The enzyme catalyzing this
is dopamine beta-hydroxylse.
03:40
And we can see in this reaction that there's
another hydroxylation that's occurring,
the hydroxyl group being added on the
top part of the molecule near the left.
03:49
In the last of these reactions, L-norepinephrine
is converted into L-epinephrine.
03:54
This reaction is a methylation that
occurs and that methyl group is donated
by the molecule S-adenosylmethionine
to produce S-adenosylhomocysteine.
04:03
The reaction is catalyzed by the enzyme
whose name you can see on the right.
04:08
The four molecules produce
some tyrosine that
I've just described or
shown on the screen here.
04:13
Now I want to describe a little
bit about each one of them.
04:15
L-DOPA is, as we saw, a
precursor to dopamine.
04:19
It is a molecule that readily
crosses the blood-brain barrier.
04:22
And it's used to treat
Parkinson's disease.
04:24
It's a very important treatment
for Parkinson's disease.
04:29
Dopamine is a very important
neurotransmitter.
04:32
It inhibits the release
of norepinephrine.
04:35
And norepinephrine is
a vasoconstrictor.
04:38
So by inhibiting the release of
norepinephrine, dopamine is a vasodilator.
04:43
Dopamine reduces insulin
production in the pancreas.
04:46
That's a very important function that
has nothing to do with the brain.
04:50
Now deficiency of dopamine is
what causes Parkinson's disease.
04:54
And that's why L-DOPA is used
to treat Parkinson's disease.
04:57
Because by getting enough
L-dopa into the brain,
one hopes that the brain
can synthesize enough
dopamine to reduce the
effects of the deficiency.
05:07
Dopamine has many, many neurological
links to other problems and pathways.
05:11
And some of these links includes
schizophrenia and ADHD.
05:16
Norepinephrine is a
very important hormone.
05:19
It also a neurotransmitter and it works
through the noradrenergic receptors.
05:25
Norepinephrine is part of what we
refer to as the fight or flight
response, which I've discussed in
other lectures in this series.
05:32
It works by increasing
the heart rate and blood
pressure and that's why it
is a vassal constrictor.
05:38
Epinephrine, also known as adrenalin is
a related compound to norepinephrine.
05:42
It also is a hormone.
05:44
And it also has actions very
similar to that of norepinephrine.
05:47
It's involved in the fight
or flight response.
05:50
And like norepinephrine, it increases
the heart rate and blood pressure.