- [Instructor] What I
think is pretty fascinating is our body is able to
maintain a very narrow and constant range of
blood glucose in our body so noticeably about 60 to
150 milligrams of glucose per deciliter of blood
and it's not important that you know this exact
number but what I think is significant is it
contrasts something like free fatty acids for example, which we'll talk about in fatty acid metabolism. Fatty acids can range almost tenfold depending on the needs of the body so they can be very high or very low but glucose always stays
within a constant range, blood glucose level
here, and it's important that this is a very constant range because there are some tissues in our body such as our brain, some of
the cells in our eyes, and our kidneys, and
even our red blood cells that rely on glucose nearly
exclusively to produce ATP. So remember once glucose
is in the blood, it can be used by any of the cells
in our body by process of cellular respiration to produce ATP. Remember the three big steps
of cellular respiration are first glycolysis,
the breakdown of glucose, and then the glucose
goes to the Krebs cycles where it undergoes some more oxidation to release all of that energy
in the glucose molecule, and finally the byproducts
of glycolysis and the Krebs cycle go to the electron
transfer chain which is able to produce ATP in bulk amount. So how does our body
keep this blood glucose in such a narrow range and
constant range in our body? Our body is able to do this differently depending on what state the body is in, so the body can be either in the FED state or something we call a fasted state. You can imagine the FED state just after you've eaten a meal. So let's say you've eaten
a chocolate chip cookie. The glucose that has been
broken up in your GI tract can then be used to
directly contribute to this blood glucose level and
then of course the glucose can be used by our cells. Now in the fasted state,
this is all the times your body is not eating,
the body has come up with two different ways to
regulate blood glucose levels. Remember in the fasting
state, our body needs way to pump glucose into the blood
to keep it at this level, essentially to replace the
glucose that's being used by our cells because we
don't have this constant intake from our chocolate chip cookie. In this case our body has
glycogen, which is a polymer, or a string of glucose
molecules that it stores away. Our body ingeniously makes
this glycogen by using some of that glucose that is dumped into our body during the FED
state, so in anticipation of knowing it's not always
going to get glucose from eating, it preserves
some of it in this glycogen molecule, and most of
this glycogen molecule is located in your liver
which is why your liver is very important for
carbohydrate metabolism. In times of fasting, our
body can actually go ahead and break down this
glycogen into the individual glucose molecules which
then can be used to keep our blood glucose levels constant. Unfortunately it turns
out that this method of breaking down glycogen
only lasts for about 10 to 18 hours in our body, that is to say after 10 to 18 hours we've
used up our glycogen stores and we need to eat another
meal to build those glycogen stores back up. You can imagine during an
overnight fast for example, it's usually about
hopefully eight to 10 hours. You can imagine there is
a point during the day where your body needs another
way of producing glucose. Our body has come up
with a second way called gluconeogenesis, which is
indeed the topic of this video. Gluconeogenesis is exactly
what its name implies. It is the genesis of creation
of neo, new, glucose. It's actually fascinating to
think about this for a moment. What we're saying in
gluconeogenesis is our body is taking precursor
molecules that are from a non-carbohydrate source,
so looks at what it has lying around and most
commonly it uses amino acids in our body as well as a
molecule called lactate which is produced as a
byproduct in exercising muscle cells, and it takes
these precursor molecules and reconfigures them to produce glucose and it's this glucose
that can then be used to be dumped into our blood to maintain constant blood glucose concentration and a constant supply
of ATP for our tissues. Now that you have a big picture
of carbohydrate metabolism and where gluconeogenesis
fits in, let's go ahead and talk about this metabolic
process, gluconeogenesis. In order to do this,
it's actually important to revisit glycolysis
briefly so I'm gonna go ahead and bring up the reaction
diagram that was used to explain glycolysis in a previous video. Just to orient you,
remember that glycolysis begins with glucose up here and glucose is broken down in a series of steps. Most notably it's broken
down into this three carbon molecule, glyceraldehyde three phosphate and then it is broken down even further and reconfigured, releasing some ATP and ADH along the way and ultimately releasing this molecule
pyruvate and pyruvate is a very important molecule
because it can continue to the Krebs cycle where it can be further oxidized to produce more
NADH that can be used by the electron transfer
change to produce ATP. Alright, so that was a big mouthful. Just remember, big picture, glycolysis breaking down glucose into pyruvate. Turns out, the way I like to think about gluconeogenesis is that
the goal of gluconeogenesis is to produce glucose
and so, gluconeogenesis is almost the exact reverse
pathway of glycolysis. We start at this end of
the reaction pathway, we start with pyruvate,
and we go funnel back the opposite direction
through all of these reactions to produce glucose. Now the key word is that it's almost the exact reverse of
glycolysis and it's almost the reverse because I
want to call attention to these orange arrows so note that there are three orange arrows,
so one from glucose to this molecule glucose six phosphate, another one here, and
then one at the very end which converts the last
molecule to pyruvate. What's important to note
about these reactions in glycolysis is that, unlike
the other bidirectional black arrows that are used
in most of the reactions, these orange arrows are unidirectional. What they're trying to
indicate is that these three reactions are irreversible. In other words, they have
a negative, if we pull out a fancy term from
chemistry, they have a negative delta g value, or
a negative Gibbs free energy which means that if we were to reverse these particular reactions we would have to flip the sign, so these
negative delta g values would be become positive
and that's problematic because we know that for
any biological reaction to occur we must have a
negative delta g value. So our body has come up with a compromise. Our body has said we have
one, two, three, four, five, six, seven reactions which these bidirectional black arrows
which are essentially reversible, that is to say
they have a delta g value that is near zero and so
they can go either direction. Our body says we'll keep
those seven reactions but I'm going from
pyruvate back to glucose we have to come up with
a different reaction pathway for the three
steps that are irreversible so that's exactly what our body did. In fact, I'll go ahead and
review in the remainder of this video but you can
say, with those three steps in mind, we're just performing
the reverse of glycolysis.
