Energy I: Metabolism, ATP, Glycolysis

Question 1

What are catabolic processes?

Answer 1

The breakdown of complex molecules to release energy

The breakdown of these produces precursors that can be used in anabolic processes

Question 2

What are anabolic processes?

Answer 2

Synthesis of new molecules from less complex components

Question 3

Why is glucose an important source of energy?

Answer 3

• ATP contains high energy phosphate bonds, and when these are broken, they release energy
• Glucose produces ATP when oxidised (as well as water and carbon dioxide)

It can also produce ATP in anaerobic conditions

Question 4

How much ATP do we require?

Answer 4

At rest - 40Kg/24hr

During exercise - 0.5Kg/min

Question 5

How does the body continue to meet the demands of ATP required?

Answer 5

Resynthesises ATP from ADP

Question 6

What are the cofactors central to metabolism?

Answer 6

NAD - nicotinamide adenine dinucleotide

FAD - flavin adenine dinucleotide

These are electron carriers used for oxidation/reduction reactions

Question 7

What is the form of oxidised NAD?

Answer 7

NAD+

Question 8

What is the form of reduced NAD?

Answer 8

NADH + H+

Question 9

What is the form of oxidised FAD?

Answer 9

FADH2

Question 10

What are the 4 major oxidative pathways?

Answer 10

• Glycolysis
• Citric acid cycle
• Electron transport coupled to oxidative phosphorylation
• Fatty acid oxidation

Question 11

What is glycolysis?

Answer 11

Splitting of 6 carbon glucose into 2X 3 carbon pyruvate molecules

Question 12

What are the products of glycolysis?

Answer 12

• 2 X 3C pyruvate
• 2X NADH molecules
• 2X ATP molecules

Produces 2X the products due to the fact that glucose splits into 2 3C compounds, and therefore the reaction must happen twice

Question 13

What is the first step of glycolysis?

Answer 13

Phosphorylation of glucose to form G-6-P (glucose six phosphate)

This results in the hydrolysis of ATP into ADP, as this phosphate will be the one that phosphorylates glucose

Question 14

What are the 2 functions of G-6-P?

Answer 14

• Maintains glucose gradient (inside + outside cell)
• Traps glucose within cell, G-6-P is unable to be transported out of cell

Question 15

What is G-6-P converted into?

Answer 15

Fructose 6 phosphate

Question 16

What is Fructose 6 Phosphate converted into?

Answer 16

Fructose 1,6 bisphosphate

This requires the hydrolysis of ATP into ADP, to provide the additional phosphate group for Fructose 1,6 bisphosphate

Question 17

What does Fructose 1,6 bisphosphate split into?

Answer 17

A 3C molecule called Dihydroxyacetone (DHAP)

A 3C molecule called Glyceraldehyde 3 Phosphate (GAP)

These molecules are in equilibrium, but the equilibrium favours the production of GAP

Question 18

What does GAP produce?

Answer 18

Phosphoenol pyruvate

This requires the reduction of NAD+ into NADH, and synthesis of ATP from ADP

Question 19

What does phosphoenol pyruvate produce?

Answer 19

Pyruvate (3C)

This requires the synthesis of ATP from ADP

Question 20

What molecules regulate glycolysis?

Answer 20

• Enzymes, catalysing irreversible reactions are potential site for regulation
• Enzymes can be regulated by:
  
  • Reversible binding of allosteric effectors
  • Covalent modification (e.g. phosphorylation)
  • Transcription (quantity of enzyme can be increased or decreased depending on gene expression)

Can be measured in terms of milliseconds, seconds, hours

Question 21

What are the enzymes that regulate glycolysis?

Answer 21

• Hexokinase
• Phospho-fructokinase
• Pyruvate kinase - this enzyme exists in number of different forms, and these different forms are distributed in different tissues - This is almost only in the liver??
  
  • Some organs such as the heart and brain do not have enzymes with allosteric binding sites, and so glycolysis would therefore not be regulated by pyruvate kinase

Question 22

What does hexokinase do?

Answer 22

Regulates first step in glycolysis, conversion of glucose into G6P

Question 23

What does phospho-fructokinase do?

Answer 23

Regulates conversion of Fructose 6 Phosphate into Fructose 1,6 bisphosphate

Question 24

What does pyruvate kinase do?

Answer 24

Regulates conversion of phosphoenol pyruvate into pyruvate

Not all organs will use this though, as they don’t all have enzymes with allosteric binding sites

Question 25

How is hexokinase activity regulated?

Answer 25

By G6P - will inhibit the further conversion of glucose to G6P, prevents too much glucose being fed through glycolytic pathway

Question 26

How is phospho-fructokinase regulated?

Answer 26

THIS IS THE MOST IMPORTANT CONTROL POINT

Regulated negatively (inhibit conversion of Fructose 6 phosphate into Fructose 1,6 bisphosphate) by:

• ATP
• Citrate
• H+

These are the end products of glycolysis and the product of respiration, if these are in abundance, there’s no need for glycolysis to be continued, and therefore no need to keep producing Fructose 1,6 bisphosphate

Regulated positively by:

• AMP - this signals the energetic state of the cell

Question 27

What inhibits phospho-fructokinase and what does inhibition of it lead to?

Answer 27

• High concentrations of ATP (lowers affinity for Fructose 6 phosphate for enzyme)
• Low pH

Inhibition of Phospho-fructokinase leads to inhibition of hexokinase, due to causing increase in glucose

Question 28

How is pyruvate kinase regulated?

Answer 28

Regulated negatively by ATP

Question 29

When is AMP produced?

Answer 29

When there are significant amounts of ADP due to high consumption of ATP, synthesis of ATP required

Enzyme Adenylate kinase converts 2 ADP molecules into ATP + AMP

Question 30

What point can galactose enter the glycolytic pathway?

Answer 30

When it’s converted into glucose, it enters at the same point glucose begins at, which would be the very beginning of glycolysis

Question 31

What point can fructose enter the glycolytic pathway?

Answer 31

• Fructose in adipose tissue can be phosphorylated into Fructose 6 phosphate, and will then enter the glycolytic pathway at that point, which would be the point at which Fructose 6 phosphate is phosphorylated into Fructose 1,6 bisphosphate
• Fructose in liver can be converted into DHAP or GAP, and will then enter at these points in the glycolytic pathway

Question 32

What does pyruvate synthesise in anaerobic conditions?

Answer 32

Lactate, in exercising skeletal muscles

• This increases acidity, therefore reducing pH, and therefore would inhibit the actions of phospho-fructokinase, so the lactate would be removed and transported to the liver for metabolisation

This requires the oxidation of NADH into NAD+, therefore generating NAD

NAD+ is required to produce ATP, and therefore, NAD+ being produced by the formation of lactate allows the glycolysis pathway to continue (until pH becomes too low), so ATP can keeps being produced

Question 33

Why do tumours use anaerobic glycolysis?

Answer 33

• As tumour size increases, need for blood supply increases, so tumour produces angiogenic factors, stimulating endothelial cells of nearby vessel to proliferate + migrate, leading to formation of vascular network
• Rate of tumour growth often too quick for scale of blood supply, so grow via anaerobic pathway