is to convert oxaloacetate into phosphoenolpyruvate
phosphoenolpyruvate
through the enzyme phosphoenolpyruvate carboxy
carboxy
kinase so big picture here the first
step is to get pyruvate
to phosphoenolpyruvate and depending on
what review source you're using or what
question bank you're using
you might see that abbreviated as pep pep
pep
phosphoenol pyruvate so pyruvate to
oxaloacetate and then oxaloacetate
to phosphoenol pyruvate now the next
step occurs later on so it's not right above
above
pep that's why i made the little arrow
have the dashed sign so somewhere
back up as you continue to progress back up
up
you have another major difference
between gluconeogenesis
and glycolysis and in this one you're
starting with fructose 1
6 bisphosphate and you're converting it
to fructose
6 phosphate so you're kind of just
chopping off that one phosphate
the enzyme that does this is fructose 1 6
6
bisphosphatase now by and large i'm a
big believer in trying to make things
stupid and simple
if you look at what you're starting with
which is fructose 1
6 bisphosphate and what you're ending with
with
fructose 6 phosphate you're really just
dropping that one phosphate like i said
so the enzyme fructose 1 6 bisphosphatase
bisphosphatase
should make perfect sense because you're
tasing off that one phosphate
so now you've got fructose 6-phosphate and
and
somewhere going back up the last major
difference between gluconeogenesis
and glycolysis is you start with glucose 6-phosphate
6-phosphate
and you convert it back to your desired
target of glucose
using the enzyme glucose 6-phosphatase
so guys and girls these three steps
which you see within these
gray boxes are the only difference
between gluconeogenesis and glycolysis
and if you want to think big picture
here the reason why there's only
these three steps that are different is because
because
the body needs gluconeogenesis when it's
in a period of fasting
and in a period of fasting there's not
readily available
atp to be used to synthesize glucose
through gluconeogenesis
after all the whole reason that the body
even wants to synthesize glucose
is because it needs to maintain
euglycemia so that we can make
glucose out of a non-carbohydrate source
to then in turn use that glucose to make
more atp
and to continue to power the cells in
our body
even in the absence of a carbohydrate source
source
so because of that the body has very
specially evolved
these three or four enzymes in gluconeogenesis
gluconeogenesis
to provide a system of checks and
balances as you might imagine if
gluconeogenesis was just going
all the time not requiring specialized regulation
regulation
at these checks then the body would be
wasting a lot of energy
and the idea is that the body's in a
fasting state already it needs more
energy it can't just be
silly willy doing gluconeogenesis so these
these
enzymes are extremely important in
protecting the cells and protecting
the very limited scarce amount of
glucose that's in the body
and in turn of atp that's in the body
so big picture lactator alanine can be
converted into pyruvate
as well as some other precursors and
then pyruvate can go back
all the way up to glucose to provide a
glucose source
from a non-carbohydrate origin to power
the cell and make more atp
now for usmle or comlex what you
absolutely need to memorize and it's the
most important thing in this video today
is that fructose 1 6 bisphosphatase is
the rate limiting step
of gluconeogenesis on these exams
the writers love to ask you what the
rate limiting step is so you absolutely
need to know
that f16bp is the rate limiting enzyme
of gluconeogenesis the other thing
that's important to know is the
regulation of these enzymes so on the
right side of this slide i'm going to
fill in the regulation now
at fructose 1 6 bisphosphatase that
enzyme is activated by citrate
but it's inhibited by amp and fructose
2-6 bisphosphate fructose 2-6 bisphosphate
bisphosphate
and amp should make a bit of sense if
you think about what's really happening
in the fed state after the after
somebody were to eat
you would undergo glycolysis because
you'd have readily available glucose
that can be broken down and recall from glycolysis
glycolysis
go watch my glycolysis video if you need
to have this explained more
but in glycolysis you see increased
levels of fructose-2-6-bisphosphate
so it should make sense to you that if
there's fructose-2-6-bisphosphate lying around
around
it's going to inhibit an enzyme involved
in gluconeogenesis
because it promotes glycolysis and you
don't want both of those pathways acting
at the same time
that would just make no sense at all down
down
for phosphoenolpyruvate carboxykinase
that step requires gtp
and at pyruvate carboxylase that step
requires biotin additionally acetyl coa
activates pyruvate carboxylase and if
you think about it
citrate and acetyl coa are both involved
in inhibiting
glycolysis so it should make a little
bit of sense that at various points in gluconeogenesis
gluconeogenesis
they actually support gluconeogenesis
lastly the big picture regulator of gluconeogenesis
gluconeogenesis
is glucagon and everything that is
glucagon genic i'm probably making that
word up but what i mean by that
is that glycolysis happens in response to
to
insulin insulin breaks down glucose and flows
flows
downward from glucose to pyruvate and
the opposite is true
of glucagon so when you don't have insulin
insulin
you have glucagon so glucagon inhibits glycolysis
glycolysis
and promotes gluconeogenesis on usmle
and comlex
much of biochemistry can be simplified
by remembering that if you have insulin
you don't have glucagon and if you don't
have insulin
you do have glucagon and therefore if
there's an enzyme that you know
is regulated by either one of those hormones
hormones
insulin or glucagon you can just think
of them as opposites
now you understand the rate limiting
enzyme and now you understand regulation
the last part of this which i'm sure
you've been wondering this entire time
is how do i remember this how do i remember
remember
the three different steps of gluconeogenesis
gluconeogenesis
that make it unique from glycolysis and
if you take a look at what we have here
working from the bottom
up or working from pyruvate back up to glucose
glucose
we have pop ffgg
pop pyruvate oxaloacetate
phosphoenolpyruvate ff for the fructoses
in fructose 1 6 bisphosphate and
fructose 6-phosphate
and the 2gs in glucose 6-phosphate and glucose
glucose
so my way of remembering this is that in
the fasting state
when gluconeogenesis would need to occur
you're going to
pop fresh gouda pop fresh gouda
right you're going to pop that fresh
cheese right in your mouth because you're
you're
fasting and you're hungry pop pop
pyruvate oxaloacetate phosphoenol pyruvate
pyruvate
the two fs for fresh fructose 1 6
bisphosphate fructose 6-phosphate
and the 2gs for gouda the g is coming
from glucose 6-phosphate
and glucose so like i said at the start
of this video
not a whole lot to know for
gluconeogenesis but if you're going to
take away a couple big picture ideas
it's glycolysis in reverse with the
exception of pop fresh gouda
the rate limiting enzyme is f16bp
and know the regulation which you see on
the right side
of this slide that's really all you need
to know and if you're comfortable with
that information you'll get all of your
questions correct
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