Topic 6. Cellular Respiration Glycolysis

CELLULAR RESPIRATION
GLYCOLYSIS
OBJECTIVES:
1. identify the major features of glycolysis
2. explain the concept of glycolysis
3. value the importance of knowing the major features of glycolysis
What is glycolysis?
Glycolysis is a series of reactions that extract energy from glucose
by splitting it into two three-carbon molecules called pyruvates.
Glycolysis is an ancient metabolic pathway, meaning that it evolved
long ago, and it is found in the great majority of organisms alive
today
In organisms that perform cellular respiration, glycolysis is the first

stage of this process. However, glycolysis doesn’t require oxygen,
and many anaerobic organisms—organisms that do not use oxygen—
also have this pathway.
Highlights of glycolysis
Glycolysis has ten steps, and depending on your interests—and
the classes you’re taking—you may want to know the details of all of
them. However, you may also be looking for a greatest hits version
of glycolysis, something that highlights the key steps and principles
without tracing the fate of every single atom. Let’s start with a
simplified version of the pathway that does just that.
Glycolysis takes place in the cytosol of a cell, and it can be

broken down into two main phases: the energy-requiring phase,
above the dotted line in the image below, and the energy-releasing
phase, below the dotted line.
 Energy-requiring phase. In this phase, the starting molecule
of glucose gets rearranged, and two phosphate groups are
attached to it. The phosphate groups make the modified sugar
—now called fructose-1,6-bisphosphate—unstable, allowing it to
split in half and form two phosphate-bearing three-carbon
sugars. Because the phosphates used in these steps come
from ATP and two ATP molecules get used up.
The three-carbon sugars formed when the unstable sugar breaks

down are different from each other. Only one—glyceraldehyde-3-
phosphate—can enter the following step. However, the unfavorable
sugar, DHAP, can be easily converted into the favorable one, so
both finish the pathway in the end.
 Energy-releasing phase. In this phase, each three-carbon

sugar is converted into another three-carbon molecule,
pyruvate, through a series of reactions. In these reactions,
two ATP molecules and one NADH molecule are made. Because
this phase takes place twice, once for each of the two three-
carbon sugars, it makes four ATP and two NADH overall.
 Each reaction in glycolysis is catalyzed by its own enzyme. The
most important enzyme for regulation of glycolysis
is phosphofructokinase, which catalyzes formation of the
unstable, two-phosphate sugar molecule, fructose-1,6-
bisphosphate. Phosphofructokinase speeds up or slows down
glycolysis in response to the energy needs of the cell.
 Overall, glycolysis converts one six-carbon molecule of glucose
into two three-carbon molecules of pyruvate. The net products
of this process are two molecules of ATP(4 ATP produced – 2
ATP used up) and two molecules of NADH.

Detailed steps: Energy-requiring

phase
 We’ve already seen what happens on a broad level during the
energy-requiring phase of glycolysis. Two ATPs are spent to
form an unstable sugar with two phosphate groups, which then
splits to form two three-carbon molecules that are isomers of
each other.
 Next, we’ll look at the individual steps in greater detail. Each
step is catalyzed by its own specific enzyme, whose name is
indicated below the reaction arrow in the diagram below.
Step 1. A phosphate group is transferred from ATP to glucose,
making glucose-6-phosphate. Glucose-6-phosphate is more reactive
than glucose, and the addition of the phosphate also traps glucose
inside the cell since glucose with a phosphate can’t readily cross the
membrane.
Step 2. Glucose-6-phosphate is converted into its isomer, fructose-

6-phosphate.
Step 3. A phosphate group is transferred from ATP to fructose-6-

phosphate, producing fructose-1,6-bisphosphate. This step is
catalyzed by the enzyme phosphofructokinase, which can be
regulated to speed up or slow down the glycolysis pathway.
Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon

sugars: dihydroxyacetone phosphate DHAP and glyceraldehyde-3-
phosphate. They are isomers of each other, but only one—
glyceraldehyde-3-phosphate—can directly continue through the next
steps of glycolysis.
Step 5. DHAP is converted into glyceraldehyde-3-phosphate. The

two molecules exist in equilibrium, but the equilibrium is “pulled”
strongly downward, in the scheme of the diagram above, as
glyceraldehyde-3-phosphate is used up. Thus, all of the DHAP is
eventually converted.
Detailed steps: Energy-releasing phase

In the second half of glycolysis, the three-carbon sugars formed in
the first half of the process go through a series of additional
transformations, ultimately turning into pyruvate. In the process,
four ATP molecules are produced, along with two molecules of NADH.
Here, we’ll look in more detail at the reactions that lead to these
products. The reactions shown below happen twice for each glucose
molecule since a glucose splits into two three-carbon molecules,
both of which will eventually proceed through the pathway.
Step 6. Two half reactions occur simultaneously: 1) Glyceraldehyde-
3-phosphate (one of the three-carbon sugars formed in the initial
phase) is oxidized, and 2 NAD⁺is reduced to NADH and H⁺. The
overall reaction is exergonic, releasing energy that is then used to
phosphorylate the molecule, forming 1,3-bisphosphoglycerate.
Step 7. 1,3-bisphosphoglycerate donates one of its phosphate

groups to ADP, making a molecule of ATP and turning into 3-
phosphoglycerate in the process.
Step 8. 3-phosphoglycerate is converted into its isomer, 2-

phosphoglycerate.
Step 9. 2-phosphoglycerate loses a molecule of water, becoming

phosphoenolpyruvate (PEP). PEP is an unstable molecule, poised to
lose its phosphate group in the final step of glycolysis.
Step 10. PEP readily donates its phosphate group to \[\text{ADP}\],

making a second molecule of ATP. As it loses its phosphate, PEP is
converted to pyruvate, the end product of glycolysis.
What happens to pyruvate and NADH?

At the end of glycolysis, we’re left with two ATP, two NADH, and two
pyruvate molecules. If oxygen is available, the pyruvate can be
broken down (oxidized) all the way to carbon dioxide in cellular
respiration, making many molecules of ATP.
What happens to the NADH?
It can't just sit around in the cell, piling up. That's because cells
have only a certain number of NAD⁺ molecules, which cycle back
and forth between oxidized NAD⁺ and reduced NADH states:
Glycolysis needs NAD⁺ to accept electrons as part of a specific

reaction. If there’s no NAD⁺ around (because it's all stuck in its NADH
form), this reaction can’t happen and glycolysis will come to a halt.
So, all cells need a way to turn NADH back into NAD⁺ to keep
glycolysis going.
There are two basic ways of accomplishing this. When oxygen is

present, NADH can pass its electrons into the electron transport
chain, regenerating NAD⁺ for use in glycolysis. (Added bonus:
some ATP gets made!)
When oxygen is absent, cells may use other, simpler pathways to

regenerate NAD⁺. In these pathways, NADH donates its electrons to
an acceptor molecule in a reaction that doesn’t make ATP but does
regenerate NAD⁺ so glycolysis can continue. This process is
called fermentation.
The following are the enzymes that catalyze different steps throughout the process of
glycolysis:
1. Hexokinase
2. Phosphoglucoisomerase
3. Phosphofructokinase
4. Aldolase
5. Phosphotriose isomerase
6. Glyceraldehyde 3-phosphate dehydrogenase
7. Phosphoglycerate kinase
8. Phosphoglycerate mutase
9. Enolase
10. Pyruvate kinase

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CELLULAR RESPIRATION

In organisms that perform cellular respiration, glycolysis is the first

Glycolysis takes place in the cytosol of a cell, and it can be

The three-carbon sugars formed when the unstable sugar breaks

 Energy-releasing phase. In this phase, each three-carbon

Detailed steps: Energy-requiring

Step 2. Glucose-6-phosphate is converted into its isomer, fructose-

Step 3. A phosphate group is transferred from ATP to fructose-6-

Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon

Step 5. DHAP is converted into glyceraldehyde-3-phosphate. The

Detailed steps: Energy-releasing phase

Step 7. 1,3-bisphosphoglycerate donates one of its phosphate

Step 8. 3-phosphoglycerate is converted into its isomer, 2-

Step 9. 2-phosphoglycerate loses a molecule of water, becoming

Step 10. PEP readily donates its phosphate group to \[\text{ADP}\],

What happens to pyruvate and NADH?

What happens to the NADH?

Glycolysis needs NAD⁺ to accept electrons as part of a specific

There are two basic ways of accomplishing this. When oxygen is

When oxygen is absent, cells may use other, simpler pathways to

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