Serine Family & Methionine Catabolism – Biochemistry | Lecturio

Serine Family & Methionine Catabolism – Biochemistry | Lecturio


The next amino acid metabolism
family I want to consider is that of the serine family. So, the serine family, as the
other families are described, uses serine as a central amino acid for branching out to make
the other amino acids. So to understand this family, I need to
first describe how serine is synthesized. There were two main pathways that
lead to serine in our cells. The first one starts
form 3-phophoglycerate. Now, this molecule, if you recall,
is found in the glycolysis pathway so we see a linkage between glycolysis
and this amino acid metabolism. The reaction starts with an oxidation of
the 3-phophoglycerate as we can see here. In this reaction, 3-phosphohydroxypyruvate
is produced as a result of that oxidation. The transamination of
3-phosphohydroxypyruvate leads to orthophosphoserine or
O-phosphoserine as we can see here. And the removal of phosphate
from O-phosphoserine results in the production of
the amino acid serine. It’s a very simple set
of steps that make that. A second way of making
serine starts with glycine. And this is a set of reactions that
I’ve described in other lectures here relating to folate metabolism. This is a very important reaction
not only for making serine but also in the reverse
direction for making glycine, as well as interchanging the formation
of different folates as we will see. So, here’s the
reaction that occurs. We start in this case with glycine and we start with this rather
complicated folate name N5, N10-methylene
tetrahydrofolate, mouthful. This reaction, a CH2OH group from
the methylene tetrahydrofolate is transferred onto
glycine to make serine. The product of that transfer
is tetrahydrofolate. So remember from folate metabolism that this is a way of interchanging
the different folates. The reaction as I said can
go on the reverse direction and the reverse direction serine is
used as a precursor to make glycine. The CH2OH group that is added to
serine is shown in the green box. The next amino acid whose
metabolism we want to consider in the serine family
is that of cysteine. Cysteine we remember is one of two
amino acids that contains a sulfur. So getting this sulfur into this serine
backbone is a central part of making cysteine. Now, cysteine can be
made in multiple ways. And when we see amino acids
made in multiple ways, it suggests first of all an interconnection
with a lot of other metabolic processes, but it also illustrates the
importance of that amino acid. Cysteine is a very important
amino acid for making proteins. The primary means of making a cysteine
is tied to the metabolism of methionine. So I’ll start with that process. If we look at methionine,
methionine of course is the other amino acid
that contains a sulfur. But methionine in this process is actually
donating a methyl group as we can see. Methionine is used to
make S-adenosylmethionine at a rather complicated
reaction that shown here. The adenylyl part of ATP
combines with methionine to make S-adenosyl methionine
or otherwise known as SAM. The enzyme catalyzing this reaction is methionine adenosyltransferase
as you can see here. In the second step of the process, S-adenosylmethionine is converted
to S-adenosylhomocysteine or SAH. Now this reaction involves the donation
of a methyl group to something else, right? It’s not going to make cystein but it’s making an intermediate
that will be used to make cysteine. That intermediate is
S-adenosylhomocysteine. The enzyme catalyzing this
reaction is transmethylase. In the next step, hydrolyzing
S-adenosylhomocysteine to release the adenosine creates
the molecule homocysteine. And I’ve drawn its structure on the right. The enzyme catalyzing this is
S-adenosylmethionine hydrolase. Now, homocysteine is an important
molecule to understand because it has numerous
health consequences. High blood levels of homocysteine is related to cardiovascular
disease and stroke risk. And so one of the things physicians will
do when they’re assessing your health is actually measure the
level of this molecule, because high levels of this
molecule are not good. In the next step, homocysteine combines
with serine to make cystathionine. Now, I’ve drawn the structure of
this molecule on the lower right. And we’ll in just a second how
cysteine is made from that. The enzyme catalyzing this reaction
is cystathionine beta-synthase. Now, deficiency of this enzyme
leads to homocystinuria. And we’ve seen that homocysteine
is not a good molecule to have. So a deficiency of this enzyme has
some pretty severe consequences for a person’s health. And the last reaction, cystathionine
is converted into cysteine Now, this reaction involves
splitting out of beta-ketobutyrate, and the splitting out of that results
in the production of cysteine. Now, this is slightly complicated so
I’ll show you that in just a second. Water is required for this process and the process, not only is the splitting
occurring that produces cysteine, but the other half of the molecule
is losing an ammonium group to become the beta-ketobutyrate. The enzyme catalyzing this
reaction is cystathionase. And we can see what has really
happened in this process. So I’ve started here to show you the
starting molecules that make cystathionine. I’ve labeled, first of all, the
serine and the homocysteine. Now, these two combine together
to make the cystathionine What happens in producing cysteine
is simply we shift where we cut. You can see that in this case that
the boxes of the green and the red are shown in the right side of the sulfur to cleave out and make cysteine
involve simply shifting the box. So the cleavage happens as shown here
and that’s what produces cysteine, as shown in the green, and beta-ketobutyrate is produced
in the molecule on the right after water cleaves
off the ammonium ion.

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