Now, tyrosine is also a precursor
of the thyroid hormones.
And this is an interesting
set of reactions that occur
in the cells of our
I'm going to step you through the process
and we'll see what happens here.
So thyroglobulin is a protein that's
necessary for making the thyroid hormones.
It literally provides a substrate
on which the individual
thyroid hormones are synthesized
as we can see here.
Thyroglobulin synthesis begins
in the endoplasmic reticulum.
And after it has been made,
it is excreted out of the
out of the cell into the
And that's the process you see with
those pink arrows moving to the left.
Thyroglobulins serve as a substrate
because sticking off of it
are the precursors of what will
become the thyroid hormones.
Those are those little hexagonal
structures that you can see
by the secreted
protein on the left.
The export from the cell, as I said,
releases the thyroglobulin out
into the extracellular space.
So, the synthesis of thyroid hormone
is not occurring inside of a cell,
it's actually outside the cell
where this process occurs.
Critical for making the thyroid
hormones is the ion iodide.
So, iodide is important for the
synthesis for the thyroid hormones.
Iodide is found in the bloodstream
and has to be moved out of the
bloodstream into the cell
and then ultimately into
that extracellular space
where it can be joined with the
precursors on the thyroglobulin.
We see that process happening
in this set of reactions.
That is first of all the
iodide in the blood
is grabbed by the sodium-iodide symporter
which moves both ions into the cell.
We see that happening.
After iodide has gotten into the cell,
it's then transported out of the cell
by another transporter moving
everything to the left.
This gets the iodide out into the
extracellular space as we can see.
And the iodide then combines
with the precursors
that are attached to the thyroglobulin
to make the thyroid hormones.
We see this iodination process
occurring right here.
And then after the iodides
have been put onto
the individual thyroid
that precursor complex with the
thyroglobulin is moved back into the cell.
Now, the thyroglobulin at
the point is broken down.
The thyroglobulin is no longer needed
and that's happening in the
next step as we can see here.
And finally, the thyroid hormones
are then moved out of the cell
and into the bloodstream where they're
used by the rest of the body.
Now, the thyroid hormones that I was just
describing are shown on the screen here.
They're known as T3 or
triiodothyronine or T4, thyroxine.
T3 is actually the more active
form of the thyroid hormones
but T4 is the more
T4 is converted into T3 by
enzymes known as deiodinases.
And by the way, the 3s and 4s
describe the number of iodines
that are in each of this molecules.
We see the difference being that
T4 has four and T3 has three.
Now an interesting
side of that about the
deiodinases is that all
the ones that are known,
all contain that very
rare amino acid selenium,
saying that amino selenium
has some important function
involving the removal of
iodine from these molecules.
Now, tyrosine metabolism is also
linked to some other molecules
that we've heard of and know of.
One of these is melanin.
Melanin is known of course
for coloring our skin
and it's produced by oxidizing and
polymerizing tyrosine as we can see here.
Now, melanin has a very
We're only looking at a part of a
melanin molecule in the structure here.
We see places where it says
and that means more of these
molecules can be attached
at the places where those
arrows actually extend out.
The tyrosine unit or one tyrosine unit
building melanin is shown in the green box.
The arrows of course
pointing to places
polymerization is occurring.
Another molecule made from
tyrosine is benzoquinone,
a very important
part of coenzyme Q.
Coenzyme Q is essential for the process of
electron transport and energy generation.
We can see the structure of
benzoquinone at the bottom
and we see also the part
that comes from tyrosine.
Now, tyrosine metabolism as we've
seen is a little complicated
that leads to a lot
of different things.
Just like the breakdown of phenylalanine
was important for healthy cells,
so too is the proper
breakdown of tyrosine.
If tyrosine breakdown is interrupted
by, for example, the lack of enzymes
needed to go through the whole process,
then there would be problems that arise.
There are four types of
tyrosinemias that arise.
Now tyrosinemia arises because the
concentration of tyrosine accumulates
because it is not being
broken down properly.
We see the breakdown process for
tyrosine in the box on the right.
There is a set of five different
steps that are involved
in getting from tyrosine to
fumurate and acetoacetate.
Now, the types of tyrosinemia that occur
relate to different enzymes that
are deficient in this pathway.
The type I tyrosinemia that
I've highlighted here,
it results from the lack of
the enzyme that converts
the very last reaction
as you can see.
Whenever we are lacking an
enzyme in a metabolic pathway,
that means that the molecules
that preceded will accumulate.
So in this case not only
will tyrosine accumulate
but so will the other four precursors;
homogentisate and the other
molecules that you can see.
Type II tyrosinemia arises from a
deficiency of the very first enzyme.
This enzyme will result in the
accumulation only of tyrosine.
Now, we could imagine that we
can distinguish these diseases
by the fact that different
molecules are accumulating
and they may have different
consequences as a result.
So, type II tyrosinemia arises
from other deficiencies
of the enzyme tyrosine
transaminase as you can see.
Type III tyrosinemia arises from a deficiency
of the next enzyme in the pathway.
So, again we see accumulation of
the two precursors prior to that.
And finally alcaptonuria, which is
also known as black urine disease,
arises from a deficiency
of the third enzyme.
So, any of these enzymes
deficient cause some problems
for other persons who has those.
Now, the treatments for both the
tyrosinemias as well as the phenylketonurias
can be handled by restricting the
amount of tyrosine and phenylalanine
that a person gets
in their diet.
A more severe way that deals with
this is by having a liver transplant.