Glycolysis: Step 1: Hexokinase

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GLYCOLYSIS

Glycolysis is the metabolic process that serves as the foundation for both aerobic and
anaerobic cellular respiration. In glycolysis, glucose is converted into pyruvate. Glucose
is a six- membered ring molecule found in the blood and is usually a result of the
breakdown of carbohydrates into sugars. It enters cells through specific transporter
proteins that move it from outside the cell into the cells cytosol. All of the glycolytic
enzymes are found in the cytosol.
The overall reaction of glycolysis which occurs in the cytoplasm is represented simply
as:
C6H12O6 + 2 NAD+ + 2 ADP + 2 P > 2 pyruvic acid, (CH3(C=O)COOH + 2 ATP + 2
NADH + 2 H+

Step 1: Hexokinase

The first step in glycolysis is the


conversion of D-glucose into glucose6-phosphate.
The
enzyme
that
catalyzes this reaction is hexokinase.
Details:
Here,
the
glucose
ring
is
phosphorylated. Phosphorylation is the
process of adding a phosphate group
to a molecule derived from ATP. As a
result, at this point in glycolysis, 1
molecule of ATP has been consumed.
The reaction occurs with the help of
the enzyme hexokinase, an enzyme
that catalyzes the phosphorylation of
many six-membered glucose-like ring
structures. Atomic magnesium (Mg) is
also involved to help shield the
negative charges from the phosphate
groups on the ATP molecule. The result
of this phosphorylation is a molecule
called
glucose-6-phosphate
(G6P),
thusly called because the 6 carbon of
the glucose acquires the phosphate
group.

Step 2: Phosphoglucose
Isomerase

The
second
reaction
of
glycolysis is the rearrangement of
glucose
6-phosphate
(G6P)
into
fructose 6-phosphate (F6P) by glucose
phosphate isomerase (Phosphoglucose
Isomerase).
Details:
The second step of glycolysis involves
the conversion of glucose-6-phosphate
to fructose-6-phosphate (F6P). This
reaction occurs with the help of the
enzyme phosphoglucose isomerase
(PI). As the name of the enzyme
suggests, this reaction involves an
isomerization reaction.
The
reaction
involves
the
rearrangement of the carbon-oxygen
bond to transform the six-membered
ring into a five-membered ring. To
rearrangement takes place when the
six-membered ring opens and then
closes in such a way that the first
carbon becomes now external to the
ring.

Step 3: Phosphofructokinase

Phosphofructokinase,
with
magnesium as a cofactor, changes
fructose 6-phosphate into fructose 1,6bisphosphate.
Details:
In the third step of glycolysis, fructose6-phosphate is converted to fructose1,6-bisphosphate (FBP). Similar to the
reaction that occurs in step 1 of
glycolysis, a second molecule of ATP
provides the phosphate group that is
added on to the F6P molecule.

This step utilizes the enzyme aldolase,


which catalyzes the cleavage of FBP to
yield two 3-carbon molecules. One of
these
molecules
is
called
glyceraldehyde-3-phosphate
(GAP)
and
the
other
is
called
dihydroxyacetone phosphate (DHAP).

Step 5: Triphosphate isomerase

The enzyme that catalyzes this


reaction is phosphofructokinase (PFK).
As in step 1, a magnesium atom is
involved to help shield negative
charges.

Step 4: Aldolase

The
enzyme
triophosphate
isomerase rapidly inter- converts the
molecules
dihydroxyacetone
phosphate (DHAP) and glyceraldehyde
3-phosphate (GAP). Glyceraldehyde
phosphate is removed / used in next
step of Glycolysis.
Details:

The enzyme Aldolase splits


fructose 1, 6-bisphosphate into two
sugars that are isomers of each other.
These
two
sugars
are
dihydroxyacetone phosphate (DHAP)
and
glyceraldehyde
3-phosphate
(GAP).
Details:

GAP is the only molecule that


continues in the glycolytic pathway. As
a result, all of the DHAP molecules
produced are further acted on by the
enzyme triphoshpate isomerase (TIM),
which reorganizes the DHAP into GAP
so it can continue in glycolysis. At this
point in the glycolytic pathway, we
have two 3-carbon molecules, but
have not yet fully converted glucose
into pyruvate.

Step 6: Glyceraldehyde-3phosphate Dehydrogenase

Glyceraldehyde-3-phosphate
dehydrogenase
(GAPDH)
dehydrogenates and adds an inorganic
phosphate
to
glyceraldehyde
3phosphate,
producing
1,3bisphosphoglycerate.
Details:
In this step, two main events take
place: 1) glyceraldehyde-3-phosphate
is
oxidized
by
the
coenzyme
nicotinamide adenine dinucleotide
(NAD);
2)
the
molecule
is
phosphorylated by the addition of a
free phosphate group. The enzyme
that
catalyzes
this
reaction
is
glyceraldehyde-3-phosphate
dehydrogenase (GAPDH).
The
enzyme
GAPDH
contains
appropriate structures and holds the
molecule in a conformation such that
it allows the NAD molecule to pull a
hydrogen off the GAP, converting the
NAD to NADH. The phosphate group
then attacks the GAP molecule and
releases it from the enzyme to yield
1,3 bisphoglycerate, NADH, and a
hydrogen atom.

Phosphoglycerate
kinase
transfers a phosphate group from 1,3bisphosphoglycerate to ADP to form
ATP and 3-phosphoglycerate.
Details:
In this step, 1,3 bisphoglycerate is
converted to 3-phosphoglycerate by
the enzyme phosphoglycerate kinase
(PGK). This reaction involves the loss
of a phosphate group from the starting
material. The phosphate is transferred
to a molecule of ADP that yields our
first molecule of ATP. Since we actually
have
two
molecules
of
1,3
bisphoglycerate (because there were
two 3-carbon products from stage 1 of
glycolysis), we actually synthesize two
molecules of ATP at this step. With this
synthesis of ATP, we have cancelled
the first two molecules of ATP that we
used, leaving us with a net of 0 ATP
molecules up to this stage of
glycolysis.
Again, we see that an atom of
magnesium is involved to shield the
negative charges on the phosphate
groups of the ATP molecule.

Step 8: Phosphoglycerate Mutase


Step 7: Phosphoglycerate Kinase

The enzyme phosphoglycero


mutase relocates the P from 3phosphoglycerate from the 3rd carbon
to the 2nd carbon to form 2phosphoglycerate.
Details:
This
step
involves
a
simple
rearrangement of the position of the
phosphate
group
on
the
3
phosphoglycerate molecule, making it
2 phosphoglycerate. The molecule
responsible for catalyzing this reaction
is called phosphoglycerate mutase
(PGM). A mutase is an enzyme that
catalyzes the transfer of a functional
group from one position on a molecule
to another.
The reaction mechanism proceeds by
first adding an additional phosphate
group to the 2 position of the 3
phosphoglycerate. The enzyme then
removes the phosphate from the 3
position leaving just the 2 phosphate,
and thus yielding 2 phsophoglycerate.
In this way, the enzyme is also
restored to its original, phosphorylated
state.
Step 9: Enolase

The enzyme enolase removes a


molecule
of
water
from
2phosphoglycerate
to
form
phosphoenolpyruvic acid (PEP).
Details:

This step involves the conversion of 2


phosphoglycerate
to
phosphoenolpyruvate
(PEP).
The
reaction is catalyzed by the enzyme
enolase. Enolase works by removing a
water group, or dehydrating the 2
phosphoglycerate. The specificity of
the enzyme pocket allows for the
reaction to occur through a series of
steps too complicated to cover here.

Step 10: Pyruvate Kinase

The enzyme pyruvate kinase


transfers
a
P
from
phosphoenolpyruvate (PEP) to ADP to
form pyruvic acid and ATP Result in
step 10.
Details:
The final step of glycolysis converts
phosphoenolpyruvate into pyruvate
with the help of the enzyme pyruvate
kinase. As the enzymes name
suggests, this reaction involves the
transfer of a phosphate group. The
phosphate group attached to the 2
carbon of the PEP is transferred to a
molecule of ADP, yielding ATP. Again,
since there are two molecules of PEP,
here we actually generate 2 ATP
molecules.
Steps 1 and 3 = 2ATP
Steps 7 and 10 = + 4 ATP
Net visible ATP produced = 2.

Immediately
upon
finishing
glycolysis, the cell must continue
respiration in either an aerobic or
anaerobic direction; this choice is
made based on the circumstances of
the particular cell. A cell that can
perform aerobic respiration and which
finds itself in the presence of oxygen
will continue on to the aerobic citric
acid cycle in the mitochondria. If a cell
able to perform aerobic respiration is

in a situation where there is no oxygen


(such as muscles under extreme
exertion), it will move into a type of
anaerobic
respiration
called
homolactic fermentation. Some cells
such as yeast are unable to carry out
aerobic
respiration
and
will
automatically move into a type of
anaerobic respiration called alcoholic
fermentation.

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