Overview of Glycolysis

Summary

This lecture delves into glycolysis, the metabolic pathway that converts glucose into pyruvate, ATP, and NADH. It's a three-stage process occurring in the cytoplasm, with stage one preparing glucose for cleavage, stage two breaking it into two three-carbon molecules, and stage three harvesting energy to form ATP. The lecture emphasizes the purpose of each stage, the enzymes involved, and the energy changes, concluding that glycolysis yields two ATP molecules per glucose molecule.

Takeaways

• 📚 Glycolysis is the metabolic pathway that breaks down glucose into pyruvate, ATP, and NADH molecules, occurring in the cell's cytoplasm.
• 🔑 Glycolysis is divided into three stages for clarity and functional specificity: Stage 1 (3 steps), Stage 2 (2 steps), and Stage 3 (5 steps).
• 🔄 Stage 1 focuses on trapping glucose within the cell and preparing it for cleavage in Stage 2, involving the addition of phosphate groups to destabilize the molecule.
• 🔬 Hexokinase initiates Stage 1 by phosphorylating glucose to form glucose 6-phosphate, using ATP and creating ADP and a hydrogen ion.
• 🔄 Stage 2, the 'cleavage stage,' involves the transformation of fructose 1,6-bisphosphate into two identical three-carbon molecules: DHAP and G3P, facilitated by aldolase.
• 🔄 Stage 3 is the 'energy-harvesting stage,' where ATP is produced and pyruvate is formed, with a focus on transferring high-energy phosphate groups.
• ⚡️ The conversion of G3P to 1,3-BPG in Stage 3 is crucial as it increases the molecule's potential to transfer a high-energy phosphate group.
• 🔋 The net result of glycolysis is the production of two ATP molecules, two NADH molecules, and two pyruvate molecules per glucose molecule, considering the energy invested and harvested.
• ⚖️ The overall process is energy-efficient as it yields a net gain of two ATP molecules after accounting for the two ATP molecules used in the initial phosphorylation steps.
• 🌟 Glycolysis is a fundamental metabolic pathway essential for energy production in cells, even under anaerobic conditions.

Q & A

What is glycolysis and where does it occur in the cell?

Glycolysis is the metabolic process that breaks down glucose into pyruvate molecules, ATP molecules, and NADH molecules. It takes place in the cytoplasm of the cell.

How many stages are there in glycolysis and what is the purpose of each stage?

Glycolysis is typically divided into three stages. Stage 1 prepares the glucose molecule for cleavage, Stage 2 involves the cleavage of glucose into two three-carbon molecules, and Stage 3 harvests energy to form ATP molecules.

What is the role of hexokinase in glycolysis?

Hexokinase is the enzyme that phosphorylates glucose, forming glucose 6-phosphate. This step traps the glucose molecule inside the cell and makes it more reactive for the subsequent steps.

Why is glucose 6-phosphate converted into fructose 6-phosphate in glycolysis?

Glucose 6-phosphate is converted into fructose 6-phosphate to create a symmetrical molecule, which is necessary for the production of two identical three-carbon molecules in Stage 2.

What is the significance of the second phosphorylation step in Stage 1 of glycolysis?

The second phosphorylation step in Stage 1, catalyzed by phosphofructokinase, further destabilizes the glucose molecule, making it more reactive and preparing it for cleavage in Stage 2.

What are the two three-carbon molecules produced from the cleavage of fructose 1,6-bisphosphate?

The two three-carbon molecules produced from the cleavage of fructose 1,6-bisphosphate are dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P).

Why is DHAP converted into G3P in glycolysis?

DHAP is converted into G3P because both are trioses (three-carbon sugars), and this conversion is necessary for the continuation of glycolysis, as G3P is the molecule that participates in the energy-harvesting reactions in Stage 3.

What is the role of GAPDH in the sixth step of glycolysis?

GAPDH (glyceraldehyde 3-phosphate dehydrogenase) catalyzes the reaction that converts G3P into 1,3-BPG (1,3-bisphosphoglycerate), using NAD+ and inorganic phosphate, and producing NADH and ATP.

How does the conversion of 3-phosphoglycerate to 2-phosphoglycerate in glycolysis affect the molecule's stability?

The conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase destabilizes the molecule, making it more reactive and preparing it for the subsequent reaction that forms phosphoenolpyruvate (PEP).

What is the final product of glycolysis and how many ATP molecules are produced per glucose molecule?

The final products of glycolysis are pyruvate molecules and a net gain of 2 ATP molecules per glucose molecule, considering the initial investment of 2 ATP molecules in Stage 1.

Outlines

00:00

🔬 Glycolysis: An Overview

This paragraph introduces glycolysis as the metabolic pathway that breaks down glucose into pyruvate, ATP, and NADH molecules. It occurs in the cell's cytoplasm and is divided into three stages, each with a specific purpose. Stage 1 involves three steps to prepare glucose for cleavage in Stage 2, which consists of two steps. Stage 3, the most complex with five steps, harvests energy to form ATP. The paragraph emphasizes the preparatory role of Stage 1 in making glucose reactive for cleavage and trapping it within the cell.

05:01

🌟 Stage 1 of Glycolysis: Investment for Cleavage

Stage 1 of glycolysis is detailed, highlighting the steps that destabilize glucose to prepare it for cleavage in Stage 2. The first step involves hexokinase phosphorylating glucose to glucose 6-phosphate, trapping it within the cell and making it more reactive. The second step is an isomerization catalyzed by phosphoglucomutase, converting glucose 6-phosphate to fructose 6-phosphate to ensure symmetry for the subsequent cleavage. The third step uses phosphofructokinase to add a second phosphate group to fructose 6-phosphate, further destabilizing it. This stage is referred to as the 'investment stage' because it consumes two ATP molecules to prepare the molecule for the energy-yielding steps ahead.

10:02

⚡ Stage 2 of Glycolysis: Cleavage and Isomerization

In Stage 2, the cleavage of fructose 1,6-bisphosphate by aldolase into two three-carbon molecules, dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P), is described. The paragraph explains the necessity of isomerization, where triose phosphate isomerase converts DHAP into G3P, ensuring that both molecules are ready for Stage 3. This stage is termed the 'cleavage stage' as it involves the actual breakdown of the six-carbon sugar into two three-carbon molecules, setting the stage for ATP production.

15:04

🏁 Stage 3 of Glycolysis: Energy Harvest and ATP Production

The final stage of glycolysis is explored, focusing on the conversion of G3P into 1,3-bisphosphoglycerate (1,3-BPG) by GAP dehydrogenase, which also reduces NAD+ to NADH. This step increases the molecule's potential to transfer a high-energy phosphate group. Phosphoglycerate kinase then transfers this phosphate to ADP, forming ATP and 3-phosphoglycerate. The subsequent steps involve phosphoglycerate mutase and enolase to transform 3-phosphoglycerate into phosphoenolpyruvate (PEP), which is high in energy. Finally, pyruvate kinase catalyzes the transfer of the high-energy phosphate from PEP to ADP, forming pyruvate and ATP. This stage is where ATP is produced, and since the reactions occur twice (once for each three-carbon molecule from Stage 2), a net gain of two ATP molecules per glucose molecule is achieved after accounting for the ATP invested in Stage 1.

🔍 Net Result of Glycolysis

The paragraph concludes with a summary of the net result of glycolysis. For each glucose molecule, two ATP are consumed in Stage 1, and four ATP are produced in Stage 3, resulting in a net gain of two ATP molecules. Additionally, two molecules of pyruvate and two NADH are produced, which can be used in other cellular processes. The paragraph emphasizes the efficiency of glycolysis in harnessing energy from glucose despite the initial investment of energy in the early stages.

Keywords

💡Glycolysis

Glycolysis is a metabolic pathway that breaks down glucose into pyruvate, generating ATP and NADH in the process. In the video, glycolysis is the central theme, with the script detailing the three stages of this process and how they contribute to cellular energy production. The script explains that glycolysis occurs in the cytoplasm and is essential for trapping glucose within the cell and preparing it for further breakdown.

💡Hexokinase

Hexokinase is an enzyme mentioned in the script that catalyzes the first step of glycolysis by phosphorylating glucose, converting it to glucose 6-phosphate. This reaction is crucial as it traps glucose within the cell and primes it for further reactions. The script uses hexokinase to illustrate the initial investment of energy in the glycolytic pathway.

💡Phosphorylation

Phosphorylation is the process of adding a phosphate group to a molecule, which is a recurring theme in the script as it describes the various steps of glycolysis. The addition of phosphate groups increases the reactivity of molecules, preparing them for subsequent reactions. For instance, the script explains how phosphorylation by hexokinase and phosphofructokinase destabilizes glucose and fructose 6-phosphate, respectively.

💡Isomerization

Isomerization is the process of converting one isomer (a molecule with the same molecular formula but different structural or spatial arrangement) into another. In the context of the video, isomerization is highlighted when glucose 6-phosphate is converted to fructose 6-phosphate by phosphoglucomutase, ensuring the molecule's symmetry required for the subsequent cleavage in glycolysis.

💡Aldolase

Aldolase is an enzyme discussed in the script that catalyzes the cleavage of fructose 1,6-bisphosphate into two three-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). This step is referred to as the 'cleavage stage' in glycolysis and is essential for producing the molecules that will be further processed to generate ATP.

💡Triose Phosphate Isomerase

Triose phosphate isomerase is an enzyme that catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). The script emphasizes the role of this enzyme in ensuring that both three-carbon molecules produced in the cleavage stage are available for the subsequent steps in glycolysis, which is critical for maintaining the pathway's efficiency.

💡Glyceraldehyde 3-phosphate (G3P)

Glyceraldehyde 3-phosphate, or G3P, is a three-carbon sugar that is a product of the aldolase-catalyzed cleavage of fructose 1,6-bisphosphate. The script describes G3P as a key molecule in glycolysis because it undergoes further reactions to generate ATP. The focus on G3P illustrates the script's aim to detail how each molecule in the glycolytic pathway contributes to energy production.

💡1,3-Bisphosphoglycerate (1,3-BPG)

1,3-Bisphosphoglycerate, or 1,3-BPG, is a high-energy intermediate in glycolysis that is formed from glyceraldehyde 3-phosphate. The script explains that 1,3-BPG has a high potential to transfer phosphate groups, which is crucial for the production of ATP. This molecule exemplifies the script's emphasis on the energy transformations occurring in glycolysis.

💡Phosphoglycerate Kinase

Phosphoglycerate kinase is an enzyme that plays a role in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, simultaneously producing ATP. The script uses this enzyme to illustrate the transition from the investment phase to the energy-harvesting phase of glycolysis, where ATP is generated from the high-energy intermediates.

💡Pyruvate

Pyruvate is the end product of glycolysis, formed after a series of reactions starting from glucose. The script describes the final steps of glycolysis that lead to the formation of pyruvate, which can then enter other metabolic pathways such as the Krebs cycle or be converted to lactate under anaerobic conditions. Pyruvate's role in the script underscores the script's comprehensive coverage of glycolysis.

Highlights

Glycolysis is the breakdown of glucose into pyruvate, ATP, and NADH molecules.

Glycolysis occurs in the cytoplasm of the cell and is divided into three stages for specific purposes.

Stage 1 of glycolysis aims to trap glucose within the cell and prepare it for cleavage in stage 2.

Hexokinase phosphorylates glucose to form glucose 6-phosphate, trapping it within the cell.

Glucose 6-phosphate is isomerized into fructose 6-phosphate to ensure symmetry for stage 2 cleavage.

Phosphofructokinase adds a second phosphate group to fructose 6-phosphate, increasing its reactivity.

Stage 2 is referred to as the cleavage stage, where fructose 1,6-bisphosphate is split into two three-carbon molecules.

Aldolase catalyzes the cleavage of fructose 1,6-bisphosphate into DHAP and G3P.

Triose phosphate isomerase converts DHAP into G3P, ensuring both three-carbon molecules are identical.

Stage 3 is the investment stage, where energy is harvested to form ATP and pyruvate.

G3P is converted into 1,3-BPG by GAPDH, generating NADH and a high-energy molecule.

Phosphoglycerate kinase transfers a phosphate group from 1,3-BPG to ADP, forming ATP.

Phosphoglycerate mutase destabilizes 3-phosphoglycerate to prepare it for further reactions.

Enolase converts 2-phosphoglycerate into phosphoenolpyruvate (PEP), a high-energy compound.

Pyruvate kinase catalyzes the transfer of a phosphate group from PEP to ADP, forming pyruvate and ATP.

The net result of glycolysis is the formation of two ATP, two pyruvate, and two NADH molecules per glucose.

Glycolysis is an essential process for energy production in cells, even under anaerobic conditions.

Transcripts

in the previous several lectures we

discuss the details of the three stages

of glycolysis so now let's actually put

all that information together into a

single lecture to actually try to make

sense of things and let's summarize our

results so glycolysis is the breakdown

of glucose into pyruvate molecules ATP

molecules and NADH molecules and all

this takes place in the cytoplasm of the

cell

now we typically break down glycolysis

into three stages we have stage 1 that

consists of 3 steps we have staged 2

that consists of 2 steps and we have the

most complex stage stage 3 that consists

of five steps now the reason we break

down glycolysis into these three stages

is because each one of these stages

actually carries out its own specific

purpose it has its own specific purpose

it carries out a specific function so

let's begin with stage one in stage one

the entire point of stage one is to take

that glucose molecule trap that glucose

molecule inside the cell so that it

can't actually leave that cell and begin

preparing that glucose molecule for

cleavage which takes place in stage two

so the entire point of stage 1 is to

prepare that molecule for stage 2 where

it basically is cleaved into two

identical 3 carbon molecules and once it

is cleaved in stage 2 it's the third

stage where we harvest some of that

energy we capture some of that energy to

form ATP molecules as we'll see in just

a moment so as we discuss each one of

these individual processes keep that in

mind because ultimately for instance in

stage one each one of these reactions

takes place and each one of these

reactions essentially wants to

accomplish that end goal so each one of

these reactions in stage 1 once the

wants the trap that molecule in the cell

and wants to destabilize the molecule

make it more reactive so that event

it is prepared for stage two to break

down into smaller molecules so let's

begin with stage one process one step

one so our glucose makes its way into

the cytoplasm of the cell what happens

is an enzyme known as hexokinase hexyl

means we have one two three four five

six carbons in our sugar kinase means

we're going to phosphorylate that

glucose so a force for group is taken

from the ATP by the hexokinase and is

added onto carbon number six and so we

form glucose 6-phosphate we break down

the ATP into ADP and also the H ion is

released as well and this reaction

releases this amount of energy so it's

an exergonic reaction that's because the

ATP is broken down into a more stable

molecule and that drives this exergonic

reaction now the point of this step is

to one destabilize the glucose to make

it more reactive and begin preparing it

for stage two and the second point is by

adding this polar component we trap that

glucose in a cell it will not be able to

exit that cell because one it can't pass

the membrane and B it cannot use any of

those transport membrane proteins

because its structure is different now

let's move on to step two in step two

the goal is to basically take that

glucose 6-phosphate and transform it

into an isomer into fructose 6-phosphate

why well because in stage two we

basically want to produce two identical

three carbon molecules and to produce

those two identical 3 carbon molecules

we have to have symmetry in our molecule

so this is not symmetric but this is

symmetric and so the glucose 6-phosphate

is transformed into fructose 6-phosphate

to make sure we get those two identical

3 carbon molecules in stage 2 so you

might ask well if I keep this molecule

the glucose 6-phosphate stage what will

happen in stage 2 well if we keep it in

the glucose that in stage 2 are going to

form one molecule that has two carbons

and one molecule that has four carbons

and that is not symmetric so that's why

we carry out step two again the entire

goal in stage one is to prepare that

glucose for cleavage which happens in

stage two and the enzyme that catalyzes

this well this is an isomerization

reaction we transform one isomer into

another and this molecule is a glucose

that contains a phosphate and so

phosphoglucomutase place spontaneously

under physiological conditions let's

look at step three so the point of step

three is to continue destabilizing that

molecule so in step one we destabilize

it increased it energy increased its

energy and made it more reactive because

we made it more polar we added a charge

and here we add a second charge and that

makes it even more reactive and more

likely to actually undergo cleavage in

stage two so we take the fructose

6-phosphate and again because we want to

add up the spoil root what type of

enzyme are we going to have well a

kinase what type of kinase well what

type of molecule isness it's a fructose

that contains a phosphate so

phosphofructokinase phosphorylates this

process and adds that was for oh group

onto this oxygen and now we have a

symmetrical molecule and once the

cleavage takes place in stage two that

will ultimately allow us to produce two

three carbon molecules and notice this

stage one because we're essentially

investing to prepare that molecule for

cleavage we actually use energy

molecules we use one two ATP molecules

in stage one that's why we call this

then

vestment stage now stage two we call the

cleavage state because this is where we

break down this molecule that we form in

stage one so we take the fructose 1 6

bisphosphate and under the guidance of

an enzyme called aldolase why aldolase

well because this is an aldol reaction

and in fact going backwards is an aldol

condensation and so that's why we call

this an aldolase so essentially what the

aldolase does is it Cleaves the bond

here and it forms these two three carbon

molecules so again the entire point of

this step was to basically create the

isomer so that once this process takes

place we produce two or three carbon

molecules and not a two carbon and a

four carbon molecule so we have two

three carbon molecules one of them is

DHAP which stands for dihydroxyacetone

phosphate and the other one is g8p which

stands for glyceraldehyde 3-phosphate

now this molecule is the one that will

go on to stage three so once we form

this gap it doesn't do anything else but

the DHAP doesn't lie directly on the

path of glycolysis and so what we have

to do is we have to take this molecule

and we have to transform it into this

molecule now just like glucose is an

isomer to fructose DHAP is an isomer to

GAAP because both of these are trioses

and a triose is a three carbon sugar so

we have one two three carbons one two

three carbons

both of these are trioses so again we

have to depend on an enzyme called

isomerase what type of isomerase will

triose phosphate isomerase trials

because these are tri OSIS and they

contain phosphate groups one each and so

triose phosphate isomerase basically

converts this GH a P the

dihydroxyacetone phosphate into the

glyceraldehyde 3-phosphate

and one stage two takes place we

essentially took so the net result of

stage two is we took the fructose 1 6

bisphosphate and we cleaned it into two

identical 3 carbon molecules these gap

molecules so let's move on to stage 3 so

essentially in this stage I've only

listed the reactions for a single gaap

molecule but you should know that all

these steps actually take place twice

because we have these two molecules that

perform in stage 2 so let's move on to

stage 3 so remember this is our

investment stage we invest energy to

prepare it for the cleavage once we

cleave it we basically go on to stage 3

and this is where this is where we're

actually going to produce those ATP

molecules and pyruvate molecules so the

entire goal here is to basically

destabilize the molecule and eventually

create a molecule that contains a high

potential to transfer force for groups

and we'll see why that's important just

the moment so let's take a look at step

6

so in step 6 what we basically want to

do is we want to transform the gap

molecule into 1 3 BPG why well because

we want to transform a molecule that has

a relatively low potential to transfer

post-oil to molecule that has a

relatively high potential to transfer

that force oil group and so we basically

take the gap we mix it with our NAD+ and

we also use a north of us an ortho

phosphate and in the presence of gap

dehydrogenase so dehydrogenase basically

means we're going to have a reaction in

which there will be a transfer of a

hydride group and so this will be

reduced into NADH we're going to release

an H ion and that phosphate the

orthophosphate will basically attack

this molecule and by onto this carbon

here and so now we have

these two phosphate groups on this

molecule so on the first position and

the third position and that's why this

molecule is essentially a molecule that

has a higher potential to actually

transfer that was Forel group and so now

in the next step we can use 1 3 BPG this

same molecule to basically transfer that

force 4 group onto an ADP molecule

thereby producing an ATP and the

molecule that catalyzes this well again

it must be a kinase why well because

this is a phosphorylation reaction and

so we use our phosphoglycerate kinase

phosphoglycerate because this is a 1 3

bisphosphoglycerate so we mix it with

the ADP because this will accept this

group here and so once the process takes

place we essentially form an ATP

molecule only for a 3 phosphoglycerate

now what happens with a 3

phosphoglycerate well in the next step

in step 8 we basically want to transform

the 3 phosphoglycerate

into a into a less stable molecule so we

want to take this and destabilize it and

that will make it more reactive so that

in step 9 it can actually react so to

destabilize this the goal is we want to

take this phosphate and bring in closer

to this negative charge so we have a

negative charge of negative 1 and a

charge of negative 2 and if we basically

decrease the distance between the

negative charge that will destabilize

this molecule and so we have an enzyme

known as phosphoglycerate mutase a

mutase is simply an enzyme that takes a

group on the molecule and changes its

position and so we have the

phosphoglycerates of phosphoglycerate

mutase will be the enzyme that will take

this group and bring it on to the second

carbon and so now we have not 3

phosphoglycerate but a 2

phosphoglycerate and notice this is an

endergonic process so under physiologic

conditions it will not be spontaneous we

have to input energy and so this

molecule will be less stable than this

molecule now so now that we have this

less stable molecule we can basically

react it in step nine and we can

transform it into a molecule that

prepares it to form that pyruvate so we

take this molecule and we use enolase to

transform it into an enol so we have

phosphoenolpyruvate or PEP we

essentially form a double bond between

these and the h and the Oh H combines

and a water is kicked off and so this is

a dehydration reaction once we form this

molecule this molecule is not very

stable and it has a very high force for

transfer potential why well because this

is essentially trapped in the enol state

and it's trapped because this oxygen

doesn't have an H it has this four spoil

group and so what must happen in the

final stages this fuzz for group must be

donated to an ADP molecule and replace

with an H and once it is replaced with

an H it can transform into the more

stable ketone state the pyruvate

molecule and that's exactly what happens

in a final stage we take the smaller

Kuehl that is high in energy so it

contains very active bonds and that

makes it a very good molecule that

actually transfers that the spore group

onto ADP and so in the presence of adp

and h plus we take this molecule and by

the action of pyruvate kinase so again

we form pyruvate in the last step and

this reaction is a phosphorylation

reaction so we're using a kinase and we

for the pyruvate in the ketone state and

that ATP molecule and because this

process takes place twice we form two

ATP molecules here we form two ATP

molecules here so a total of four ATP

molecules in stage 5 we use two ATP

molecules in stage one and the neck

result is we form two ATP molecules in

glycolysis per glucose that we actually

use up so if we sum all these individual

reactions and we basically sum up all

these individual energy values keep it

in mind that all these take place twice

and so we have to multiply these energy

values by two for these five steps we

basically get the following net result

so we have a glucose we have two adp we

have two nad plus we have two P eyes

that's our net input and then that

output is