NM - Anaerobic Metabolism

Question 1

Describe the function of the glycolysis pathway.

Answer 1

It is the most important metabolic pathway, and is present in all tissues and all organisms.

Function:

• synthesis of ATP
• using glucose and fuel

Question 2

List some examples of disaccharides.

Answer 2

Sucrose: Glucose and Fructose

Lactose: Galactose and Glucose

Maltose: Glucose and Glucose

Question 3

Describe the structure of glucose.

Answer 3

There are two forms of glucose, D-glucose (linear form) and α-D-Glucopyranose (ring form).

The carbon 1 on top of the linear form has an aldehyde functional group, and they are very reactive, so glucose can modify proteins.
Some sugars are very reactive, and are dangerous if not properly controlled.

The aldehyde can also react with a carbon on the same molecule, creating the ring form of glucose (the more common form).

The alpha-hydroxyl on the ring form on the right is in the alpha configuration (with it on the bottom) – if it goes on the top, we get the beta configuration.

Question 4

What are some sources of glucose for glycolysis?

Answer 4

• sugars & starch (polysaccharides) from diet
• breakdown of stored glycogen (the storage form of polysaccharides) from the liver
• recycled glucose (from lactic acid or amino acids or glycerol)

Question 5

The 10 Reactions of glycolysis can be grouped into 4 stages.

What are they?

Answer 5

• Activation (using up ATP )
• Splitting the 6 C sugar into half
• Oxidation (removing 2H atoms)
• Synthesis of ATP

Question 6

Describe the activation stage of glycolysis (3 reactions).

Answer 6

Reaction 1 –
Glucose -> Glucose-6 phosphate
(ATP -> ADP)

uses Hexokinase

We need to keep glucose in the cell, so we charge the glucose by adding a phosphate group.

Reaction 2 –
Glucose-6 phosphate ⇌ Fructose-6-phosphate

uses Phosphoglucose
isomerase

We convert the glucose-6-phosphate to fluctose-6-phosphate, which makes the compound easier to cleave.

Reaction 3 –
Fructose-6-phosphate -> Fructose 1,6-biphosphate
(ATP -> ADP)

uses Phosphofructokinase

We destabilise the compound by adding another phosphate – we now have two negative charges on a small molecule, which will repel each other

Question 7

Describe the splitting of the 6C sugar stage of glycolysis (2 reactions, continuing from 3 before).

Answer 7

Reaction 4 -
Fructose 1,6-bisphosphate -> Glyceraldehyde 3-phosphate

OR

Fructose 1,6-bisphosphate -> Dihydroxyacetone phosphate

both use Aldolase A

The phosphates are split equally, and one molecule gets an aldehyde group, whilst the other gets two ketone groups.

Reaction 5 -
Glyceraldehyde 3-phosphate ⇌ Dihydroxyacetone phosphate

uses Triose Phosphate isomerase

This allows the two molecules to interchange between each other.

Question 8

Describe the oxidation stage of glycolysis (1 reaction, continuing from 5 before).

Answer 8

Reaction 6 -
Glyceraldehyde 3-phosphate ⇌ 1,3-Bisphosphoglycerate
(NAD+ + Pi -> NADH + H+)

uses Glyceraldehyde- 3-phosphate dehydrogenase

Again, we are destabilising the molecule by adding another phosphate molecule.

It is an oxidation because we go from an aldehyde to an acid.
In a way, we are storing the hydrogen in that coenzyme, NADH.

There is a high energy bond between the carboxylic group and the phosphate, and that is critical to what happens next.

Question 9

Describe the ATP synthesis stage of glycolysis (4 reactions, continuing from 6 before).

Answer 9

Reaction 7 –
1,3-Bisphosphoglycerate ⇌ 3-Phosphoglycerate
(ADP -> ATP)

uses Phosphoglycerate
kinase

Here, we see the activated phosphate is shifted to the ADP to make ATP.

Reaction 8 –
3-Phosphoglycerate ⇌ 2-Phosphoglycerate

uses Phosphoglycerate
mutase

Here, the phosphate group is shifted on the molecule.

Reaction 9 –
2-Phosphoglycerate ⇌ Phosphoenolpyruvate
(-> H2O)

uses Enolase

Here, you remove water and introduce a double bond.

Reaction 10 –
Phosphoenolpyruvate ⇌ Pyruvate
(ADP -> ATP)

uses Pyruvate kinase

Here, we transfer the (now active) phosphate to ADP again.

Question 10

What are the ATP yields from glycolysis?

Answer 10

In the early stages we used 2 ATP, and in the later stages we make 4 ATP.

There is a net yield of 2 ATP.

Question 11

Describe anaerbic glycolysis.

Answer 11

When oxygen supplies to the tissues are limited, pyruvate is not metabolised to CO2.

Instead, pyruvate is converted to lactate in order to convert the cofactor NADH back to NAD+

pyruvate + NADH + H+ → NAD+ + lactate

This reaction is acatalysed by Lactate Dehydrogenase.

In the liver, we get the reaction favouring L-lactate, and in the liver, we get the reaction of L-lactate back into pyruvate.

Question 12

How is glycolysis used in skeletal muscle?

Answer 12

It produces ATP during intense exercise.

Question 13

How is glycolysis used in red blood cells?

Answer 13

It is the only pathway for ATP production (as the RBCs have no mitochondria)

Question 14

How is glycolysis used in the brain?

Answer 14

It is a major source of ATP for the brain (as it cannot use fats as fuels).

Question 15

How is glycolysis affected by the fed and fasting state?

Answer 15

We get an increased rate of glycolysis after:

• intense muscle work & exercise
• a high carbohydrate meal (high insulin levels)

We get a decreased rate of glycolysis during:
- the fasting state
(when there are high levels of circulating glucagon)

Question 16

What is the negative control of the glycolysis pathway?

Answer 16

The feedback inhibition of this metabolic pathway is by allosteric control of the enzyme phosphofructokinase.

It is the slowest step of glycolysis, and thus is the rate-limiting step.

We can use substances to slow down the rate of action of the enzyme, thus controlling the rate of the pathway,

Examples of substances that negatively affect the enzyme activity is ATP, citrate. On the other hand, AMP increases the rate of action of the enzyme.