NOTES TO REMEMBER: Glycolysis can be divided into two phases:

 Lack of antidiuretic hormone (ADH): Leads 1. Energy-consuming phase

to Excessive urination 2. Energy-producing phase.

The cell needs to spend some energy before it can

 Fat-soluble vitamins are A, D, E, K start making energy, and like any good investment the
cell gets more energy back than it puts in.
 Arachidonic acid - Naturally occurring lipids
in animals The Energy-consuming phase - requires ATP

 The function of glucagon: Increase the The Energy-producing phase - generates ATP
blood glucose - Other molecules like reduced nicotinamide
adenine dinucleotide, or NADH, which can be
 Major groups of protein in our plasma: used to make ATP.
Albumin - We can keep track of all of this using an energy
Fibrinogen counter.
Globulin

 Protein molecules in the blood:
Albumin
Gamma 1 globulin
Alpha 1 lipoprotein
Beta 1 lipoprotein
Fibrinogen
Hemoglobin.
GLYCOLYSIS
 the breakdown of glucose by enzymes, releasing
energy and pyruvic acid.
 To pull energy out of the glucose in the food it
requires glycolysis.
 A series of enzymatic reactions in which glucose, a
6-carbon sugar molecule, is broken down into (2)
two 3 carbon pyruvate molecules.
 As glucose gets processed, → Energy is produced in
the form of → adenosine triphosphate, (ATP).
 Glycolysis happens in the cytoplasm of cells , and no
special organelles or even oxygen are needed to
turn glucose into ATP.
 All cells can use glucose to make energy;
 It’s possible to do glycolysis even when oxygen
levels are low.
Going back to that delicious pizza (FOOD)
1. Pizza will enter the mouth and goes down towards
the small intestine.
2. In response to high blood glucose, →the pancreatic
beta-cells secrete →insulin.
3. Now, for glucose to get inside the cells, → it utilizes
glucose transporters, or GLUT, → which are on the
cell membrane.
(Expound how insulin attach to the cell membrane)
Note:
Some GLUTs like GLUT2 in the liver and pancreatic
beta-cells → are particularly responsive to glucose in
the presence of insulin.
4. Once glucose gets inside the cell, → it’s prevented
from diffusing across the cell membrane back into
the circulation by enzymes called → KINASES which
→ phosphorylate the glucose. Adding a phosphate
group changes the shape of the glucose molecule.
The phosphate comes from the breakdown of ATP →
into ADP and phosphate -→ so this initial
phosphorylation step drops us to -1 on that energy
counter.
Specifically, there are two enzymes called
HEXOKINASE AND GLUCOKINASE, and they both → add
a phosphate group to the 6th carbon in the glucose
molecule, →turning it into glucose-6-phosphate.
* Remember: Both enzymes pretty much do the
same thing, but
 Hexokinase →is found in all cells, whereas
 Glucokinase→ like GLUT2, →is induced by the
presence of insulin, and is found in the liver
cells and the beta-cells of the pancreas.
This first step is irreversible, → meaning that the
reaction can only go in the glucose to glucose-6-
phosphate direction, and not vice versa.
5. Glucose-6-phosphate is converted to its isomer , →
fructose-6-phosphate by an enzyme called
PHOSPHOGLUCOISOMERASE.
So, at this point, it’s still a 6-carbon molecule.
* Remember:
Fructose-6-phosphate is then → phosphorylated by
the enzyme PHOSPHOFRUCTOKINASE-1, OR PFK1, →
which adds a phosphate group to the 1st carbon on the
fructose molecule, making fructose-1,6-bisphosphate.
This is the second irreversible reaction in glycolysis →
and it also uses ATP as a phosphate source → so we’re
at -2 on that counter now.
This reaction is considered the rate-limiting step of
glycolysis →meaning that how fast PFK1 converts
fructose-6-phosphate →to fructose-1,6-bisphosphate
determines the speed at which all of glycolysis happens.
Because of this, cells closely regulate PFK1 activity by
using another enzyme, called phosphofructokinase 2 -
or PFK2.
You see - PFK2 can also phosphorylate fructose-6-
phosphate - but it adds phosphate to the 2nd carbon
instead, making fructose 2,6-bisphosphate. PFK2
activity varies depending on the level of glucose in the
blood.
When the body is well-fed; like right after eating that
slice of pizza, → blood glucose levels go up, and the →
pancreas secretes insulin, which → activates PFK2 -
resulting → in more fructose-2,6 bisphosphate.
Now, here’s the key - → increased levels of fructose-
2,6 bisphosphate → activates PFK1, which means → it
increases the rate of available PFK1 enzymes.
So, more PFK1 means that → the slowest step in
glycolysis speeds up, and more glucose is turned into
energy.
Now, when the body is in a fasting state; like a few
hours after a meal, → blood glucose goes back down,
and → the pancreas secretes glucagon instead of
insulin. Glucagon →prevent PFK2, resulting in → less
fructose-2,6-bisphosphate, which → prevents PFK1,
decreasing the rate of PFK1 enzymes, and that → slows
down glycolysis.
PFK1 is also prevented in other ways. For example,
when cells are in high energy states, → there is a lot of
ATP floating around as well as citrate, because → that’s
a by-product of fatty acid synthesis. Both ATP and
citrate prevents PFK1, because → cells that have lots of
energy don’t need to generate even more. Now when
cells do need energy, PFK1 becomes very active in
generating fructose1,6 bisphosphate.
6. Fructose 1,6 bisphosphate is cleaved by the enzyme
ALDOLASE into two 3 carbon molecules,
glyceraldehyde-3-phosphate, or G3P, and
dihydroacetone-phosphate, or DHAP.
Only G3P can go down the glycolysis pathway, so an
isomerase enzyme converts DHAP into G3P.
As a result, for each glucose molecule, there are two
G3P molecules.
7. Each G3P is converted into 1,3
bisphosphoglycerate, or 1,3-BPG, by an enzyme
called G3P-dehydrogenase.
G3P-dehydrogenase has 2 roles, it removes a hydrogen
from G3P and gives it to a nearby NAD+ molecule,
making NADH as a byproduct. It also adds a phosphate
group to the 1st carbon of G3P, making 1,3-BPG.
Now since there are two G3P molecules, this
happens twice, resulting in two NADH molecules. Each
NADH molecule enters the electron transport chain in
the mitochondria and makes roughly 3 ATP.
8. An enzyme called PHOSPHOGLYCERATE KINASE,
removes a phosphate from the 1st carbon of 1,3-
 BPG and gives it to ADP, making 3-
phosphoglycerate, and ATP as a byproduct.
9. So, we’ll add two ATPs to our counter because this
reaction happens twice – so we’re back at 0. Next,
an enzyme called a MUTASE moves the phosphate
on 3-phosphoglycerate to the 2nd carbon, making
2-phosphoglycerate.
10. After that, an enzyme called enolase removes a
water molecule from 2 phosphoglycerate and
makes phosphoenolpyruvate - or PEP.
11. Finally, the enzyme PYRUVATE KINASE transfers a
phosphate from PEP to ADP, making pyruvate, and
ATP as a byproduct.
This is our 3rd and last irreversible reaction of
glycolysis, and again we’ll add 2 ATPs to our counter
because this reaction happens twice. As it turns out,
pyruvate kinase is also regulated by the cell.
Interestingly, fructose-1,6 bisphosphate upregulates
pyruvate kinase - a process called feed-forward
regulation, because it’s sort of like one enzyme priming
another one because it’s clear that things are about to
get busy.
That’s because pyruvate can enter the mitochondria
and participate in the Krebs cycle, also called the citric
acid cycle, and the electron transport chain to make
more ATP.
And in the end, after all the mitochondrial reactions,
you’ll end up with a net total of roughly 30 to 32 ATPs.
Some cells don’t have access to sufficient oxygen; like
an exercising skeletal muscle cell, or a red blood cell
that lacks mitochondria.
In those situations, the cell can use the ENZYME
LACTATE DEHYDROGENASE to remove hydrogen from
an NADH molecule and give it to pyruvate, creating
lactate, and NAD+ as a byproduct.
NAD+ is crucial because it’s needed to work with
G3P-dehydrogenase and keep glycolysis going.
Now, normally, lactate is removed from our blood by
the kidneys.
However, if local lactate levels rise too quickly, it can
sometimes build-up, and it’s responsible for some of the
muscle soreness you develop when you exercise.

On the other hand, high levels of ATP and the amino

acid alanine downregulates pyruvate kinase activity.

Alanine comes from skeletal muscle breakdown

when fasting, and it’s used as a substrate for making
new glucose.

So high levels of alanine signify that the body needs

to make new glucose, not break it down in glycolysis.

Once pyruvate is made, glycolysis is pretty much

over.

Until this point, the process has worked without the

need of oxygen, so glycolysis is anaerobic.

And to this point, we’ve generated a total of two

ATPs in this process.

So, although this is a good investment, it’s not a great

one.

Fortunately, most cells have mitochondria, and have

access to oxygen - because that’s where the payoff
really becomes obvious.