The Catabolism of Glucose (Glycolysis)

Question 1

What is the definition of metabolism?

Answer 1

All chemical reactions that maintain the living state of cells and organisms.

Question 2

What types of reactions does metabolism consist of?

Answer 2

Anabolic and Catabolic reactions.

Question 3

What are anabolic reactions?

Answer 3

Assimilation of molecules and complex structures from the building blocks of life.
Requires energy.

Question 4

What are catabolic reactions?

Answer 4

Breakdown of molecules to obtain the anabolic “building blocks” of life and substrates for energy.
Breakdown of molecules to yield energy.

Question 5

Where does out energy come from?

Answer 5

Ultimately, all our energy comes from the sun.
Plants synthesise macromolecules, using sunlight as energy.
Catabolic pathways oxidise macromolecules, thereby creating ATP.
ATP can be used to drive biosynthetic reactions.

Question 6

Why is glucose the most important carbohydrate?

Answer 6

More than half of all organic carbon is in three polysaccharides:
Starch and cellulose, both used in plants. And glycogen (glucose in a polymer source) used in animals.

Question 7

Why is glucose considered our primary energy source?

Answer 7

Oxidised to CO2 and H2O.

Question 8

What cell types require glucose as an energy source?

Answer 8

Erythrocytes
Retina
Renal Medulla
Brain (the brain accounts of about 20% of the oxygen requirement in a resting person although it represents only about 2% of the body weight).
All cancer cells

Question 9

What is the structure of glucose?

Answer 9

Glucose has 6 carbons and you will very rarely find it in a straight chain, More likely you will find glucose forming a hexagon shape.

Question 10

What determines if a polysaccharide can be used in the body?

Answer 10

Alpha and beta bonds determine whether a polysaccharide can be used in the body.

Question 11

What are the different fates of glucose?

Answer 11

Storage
-Glycogen
- Starch
- Sucrose
- Conversion to lipids
Oxidation through Aerobic glycolysis
- Pyruvate, efficient ATP production by oxidative metabolism.
Fermentation by Anaerobic Glycolysis
- Lactate, rapid inefficient ATP production
Oxidation through the Pentose Phosphate Pathway
- Ribose-5-Phosphate, precursor for nucleotide synthesis and DNA repair, essential for growth

Question 12

What are the Intracellular stages of metabolism?

Answer 12

Stage 1 is essentially eating the food.
Stage 2 is Acetyl-CoA production.
Stage 3 Acetyl-CoA oxidation
Electron transfer and oxidative phosphorylation

Question 13

How is glucose transported into cells?

Answer 13

Via NA+/glucose symporters
Via passive facilitated diffusion glucose transporters
- GLUT 1, Brain, Low KM (M is subscript)
- GLUT 2, Liver, High KM, insulin independent, Beta-cells
- GLUT 3, Brian, Low KM
- GLUT4, Muscle, Insulin-dependent, Adipose tissue
- GLUT 5, Gut, Fructose transport
(The brain works at low glucose concentration so that even at low glucose concentration, it will carry on working and tell you to eat.
The liver works at high KM, to convert it into insulin and store it.)

Question 14

What is KM (M is subscript)?

Answer 14

The concentration at which you reach half the maximum.

Question 15

How does GLUT 1 carry out it’s role as a glucose transporter?

Answer 15

Binding of glucose to the outside triggers a conformational change.
Binding site faces inwards.
Glucose can be released in the inside.
Conformational change regenerates the binding site on the outside.

Question 16

What is glycolysis?

Answer 16

He initial pathway for the conversion of glucose to pyruvate.
(glucose + 2ADP + 2Pi + 2NAD+) -> (2pyruvate + 4ATP + 2H2O + 2NADH +2H+)
Once glucose is inside the cells it’s converted into pyruvate.

Question 17

What is the process of glycolysis?

Answer 17

In the 1st step glucose is destabilised and so activated by giving it phosphates. Which converts it into fructose-1,6-bisphosphate.
This is less stable than glucose and can easily be broken down into 2 triose phosphates.
These can then be further metabolised to create 2 pyruvate, 4 ATP and 2NADH + 2H+.

Question 18

What are the 3 stages of glycolysis?

Answer 18

Stage 1: glucose is trapped and destabilised.
Stage 2: 2 interconvertible 3-carbon molecules are formed.
Stage 3: generation of ATP.

Question 19

What is the difference in symmetry between glucose and fructose?

Answer 19

Fructose has 2 carbons that sit above the plane and glucose has 1. Therefore fructose is more symmetrical.
Fructose has 2 phosphates however so is less stable.

Question 20

What are the 2 major cellular needs of glycolysis?

Answer 20

Production of ATP.

Provision of building blocks for synthetic reactions.

Question 21

What are the 3 control points of glycolysis?

Answer 21

The control points occur where enzymes are catalysing irreversible reactions.
1. Hexokinase - substrate entry
2. Phosphofructokinase - rate of flow
3. Pyruvate Kinase - Product exit.
(The middle step is regulated because it converts fructose 6 into fructose-1 because the latter is unstable so it makes sense to not covert something stable back into something unstable unless it is going to be used).
(Each step is regulated by numerous molecules)
(If the system is backed up and not flowing quickly, you et an accumulation of glucose-6-phosphate).

Question 22

What are the irreversible/controlled reactions in glycoysis

Answer 22

Hexokinase
glucose + ATP -> glucose 6-phosphate + ADP + H+
DeltaG = -33.5 kJ mole-1
Phosphofructokinase
fructose6-phosphate + ATP -> fuctose1,6-bisphosphate + ADP + H+
DeltaG = -22.2 kJ mole-1
Pyruvate kinase
phosphoenolpyruvate + ADP + H+ -> pyruvate + ATP
DeltaG = -16.7 kJ mole-1
These 3 reactions are regulated because they are irreversible reactions. Enzymes that control reactions with large free energies make good control points.

Question 23

What is phosphofructokinase?

Answer 23

Key enzyme controlling rate of substrate movement along glycolytic pathway.
fructose6-phosphate + ATP -> fructose1,6-bisphosphate + ADP + H+

Question 24

What effect do AMP and fructose2,6-bisphosphate have?

Answer 24

Will increase glycolysis if energy is needed.

Question 25

What effect does ATP have on glycolysis?

Answer 25

Will slow down glycolysis if energy abundant.

Question 26

What effect will citrate have on glycolysis?

Answer 26

TCA cycle intermediate. Slows downstream pyruvate entry to TCA cycle if energy abundant.

Question 27

What effect does H+ have on glycolysis?

Answer 27

Slows down glycolysis if too much lactic acid is being produced.

Question 28

How does energy change control phosphofructokinase?

Answer 28

The ATP/AMP ratio is called the energy change
- is all adenylate nucleotides are in the shape of ATP, the cell is fully “charged”.
- If the cell only contains AMP and Pi, it is “discharged”.
Why is AMP and not ADP the positive regulator?
- if ATP is rapidly used up ATP -> ADP +Pi
adenylate kinase can salvage some of the energy in ADP
2ADP -> ATP + AMP
(If everything is in the form of full charge, then it is fully charged and if everything is in the form of AMP and Pi it is fully discharged).

Question 29

What do the 2 pyruvate from glycolysis go on to do?

Answer 29

They go on to fuel the TCA cycle in mitochondria.

Question 30

What happens if mitochondrial metabolism is inhibited by lack of oxygen?

Answer 30

NADH is used to ferment pyruvate to lactic acid (lactate).
NADH is re-generated at beginning of stage 3.
(If the cell doesn’t have enough oxygen, the production of ATP is less efficient.
Oxidated phosphorylation means that it needs oxygen.
In fermentation instead pyruvate accepts the electrons from NADH and recycles it. For each of the pyruvate, they each recycle one NADH to NADs.
This means that you can keep making a little bit of energy.

Question 31

What is the Warburg Effect: Up-regulation of anaerobic glycolysis in cancer cells?

Answer 31

Cancer cells produce energy by high rate of glucose metabolism to lactate (anaerobic glycolysis).
Cancer cells have low KM Hexokinase

Question 32

What are the advantages and disadvantages of the Warburg effect?

Answer 32

Advantages
- Rapid energy production
- Supports other pathways for nucleotide synthesis (needed for growth)
- Supports rapid cell growth (proliferation)
Disadvantages
- Produces H+ and lactate as end products
- Very inefficient ATP synthesis
- High glucose consumption demand
- Cancer patients lose weight
(Cancer cells preferentially utilise glucose as an energy source and se it anaerobically meaning they produce lactate.
A low KM for hexokinase means that as soon as they get a little bit of glucose, they start to generate energy rapidly.
Glucose can go into the pentose phosphate pathway which is also important for the replication of DNA of cancer cells.
Hey produce protons and lactate as the end products and are inefficient at producing ATP.
This is why cancers kill people as they compete with the patient for energy and consume all the energy of the patient).

Question 33

You can treat cancer by targeting glycolysis. what stages of glycolysis are targeted?

Answer 33

2-Deoxy-glucose
Competitive inhibitor. Blocks further metabolism of G6P.
3-Bromopyruvate Competitive inhibitor. Blocks production of 1,3 bisphosphoglycerate.
Dichloroacetate Promotes conversion of lactic acid to pyruvate. By re-engaging mitochondrial metabolism it slows glycolytic rate. Cells can no longer sustain nucleotide synthesis and so cannot grow.
(Dichloroacetate stops the pentose phosphate pathway and so the cancers cannot replicate).