So I said folate is can sort of
be recycled among each other
and now I want to spend some time talking
about how that recycling process
between different folate
molecules actually occurs.
We start this process looking at
the very bottom of the screen
where we start with the tetrahydrofolate
that we’ve been talking about so far.
Tetrahydrofolate can be converted
into the methylene form,
the N5, N10 methylene form
that I described earlier
via the serine/glycine metabolism,
reactions that we saw earlier.
These reactions add in the
direction of the methylene.
They add methylene group
between those two nitrogens
as we saw before by
converting serine to glycine.
The methylene form can be converted
into a methyl form by reduction
as we can see in the next slide and that
reduction requires electrons from NADPH.
That produces the N5 methyl group.
We can see that we now
have a methyl group
in place of the methylene
group that we had before.
The methionine synthesis, of
course, uses this N5 methyl THF
to be able to produce the
THF that we saw earlier.
And this will be closed to the cycle
on that round of the folate molecules.
The N5, N10 methylenetetrahydrofolate
can also be converted
into a group of other
folates as we can see here.
That happens if it gets oxidized.
So oxidation of that methylene
group, donating electrons into NADP
to make NADPH produces this N5, N10
methenyltetrahydrofolate or THF
as you can see on the screen.
This molecule has now this carbon double
bonded to the nitrogen as you can see.
The restructuring of that
molecule produces another folate
known as the N5 formyl
tetrahydrofolate as shown
and the formyl group is shown
in the blue box contrasted with
the methenyl group that we’ve shown above.
So tetrahydrofolate can also be converted
into N5 formyl tetrahydrofolate
by adding a formyl group that comes from
an amino acid metabolism of histidine.
Histidine is converted into 4-amino
glutamic acid during its breakdown process
and that 4-amino glutamic acid is
the source of the formyl group
in making the N5-formyl
Well that’s a lot different
things that are happening,
but those aren’t even the
only ones that happened
with the N5, N10
The imino group -- that is
imino, I-M-I-N-O group --
can be swapped as we see in
the reaction moving from
the N5,N10 methenyltetrahydrofolate
into the N5 4-amino
tetrahydrofolate as shown here.
And we see again a slight
difference in configuration
of the carbon attached to
those two nitrogen molecules.
We also see, of course, that the
tetrahydrofolate can be formiminated
but using formyl glutamic acid
and producing glutamic acid
to produce the N5 4-amino
And last but not the least, we see
the N5-N10 methenyltetrahydrofolate
can be hydrolyzed and lose
its group as we see here
forming the N10 formyl
and the alternate pathway to get
into that is from tetrahydrofolate
which combines with
the formate and ATP
to add the formate group as we can see
in the very last reaction shown here.
So folate as I said earlier is important in
the diet, it’s important for human health.
It can’t be made by humans and therefore
the only source we have is in our diet.
In the late 20th century, it was
discovered that deficiencies of folate
in pregnant mothers led to
neural tube defects in infants.
And it was that discovery that led
to the supplementation of folates
in food sources or food
stuffs like breads.
Deficiency of folate is also associated
with the variety in other health problems
including heart palpitations,
damage to nerves,
shortness of breath,
and other things associated with
the mouth and peptic ulcers.
Deficiencies of folate can
also lead to mental problems
including confusion, forgetfulness,
depression and behavioral disorders.
Well, we’ve covered a lot of territory here,
both the fat-soluble vitamins K and E
and the two most important sets
of molecules for the movement
and for the source of single carbon
atoms in biochemical processes.