Lecture 31 - Energy I Metabolism, ATP, Glycolysis

Question 1

Life processes involved in metabolism (4)

Answer 1

o Synthesis of new molecules
o Establishing ion gradients
o Mechanical work
o Keeping warm

Question 2

Catabolism (1)

Answer 2

Breakdown of complex molecules to release energy or carry out mechanical work.

Question 3

Anabolism (2)

Answer 3

Synthesis of new molecules from less complex components.

Biosynthesis of aa, nucleotides, sugar, fats from precursors for growth, repair and movement).

Question 4

Why should we study metabolism? (4)

Answer 4

Understand the metabolic basis for disease.
Diseased state changes the way the body uses food.
Compare how the body normall processes the nutrients, to understand the change.
Use changes in metabolites to aid diagnosis and to follow treatment.

Question 5

Examples of metabolic diseases (4)

Answer 5

Diabetes
Atherosclerosis
Gall stones
Cancer

Question 6

Energy provision (ATP) (9)

Answer 6

Bodies energy provision.
Acceptor and donator of energy.
Short term reservoir of energy.
High energy phosphate bonds.

Hydrolysis of ATP is 65 kJ/mole.
At rest = 40 kg/24 hours.
During exercise = 0.5 kg/min.

Body only contains 100g of ATP, it is re-synthesised from ADP.
Largely done through oxidative phosphorylation in the mitochondria.

Question 7

Major oxidative pathways (4)

Answer 7

• Citric acid cycle (Krebs/TCA Cycle)
• Electron transport coupled to oxidative phosphorylation
• Fatty acid oxidation
• Glycolysis

Question 8

What regulates glycolysis? (3)

Irreversible reactions are potential sites for regulation. These enzymes can be regulated by….

Answer 8

Reversible binding of allosteric effectors- binding of molecules to sites other than active site, commonly product of that particular pathway.
Covalent modification (e.g. phosphorylation).
Transcription (over a long time enzyme made will change).

Question 9

Regulating enzymes - PFK (7)

Answer 9

If PFK is inhibited so is glycolysis.
End products (e.g. ATP) can regulate activity of PFK (converting fructose-6-phosphate to fructose 1,6 biphosphate).
High conc of ATP = Lower affinity of fructose-6-phosphate.
PFK is inhibited by citrate (made in Krebs cycle) and H+ (low pH due to lactate build up in muscles) - they indicate amount of glucose going through glycolytic pathway.
PFK is stimulated indirectly by build-up of G6P.
Positive regulation of PFK by AMP (product of conversion of ATP –> ADP) and fructose 2,6 biphosphate - shows energy level in cell.

Question 10

Regulating enzymes - Glucokinase (7)

Answer 10

Used in the liver
Not affected by G6P build-up.
High Km = More glucose required.
Low affinity for glucose.
Active at higher concentrations of glucose.
Slows down glycolysis.
Livers function in terms of glucose metabolism is to get excess glucose —-> Glycogen for storage. This enzyme allows it to do this.

Question 11

Regulating enzymes - Hexokinase (5)

Answer 11

Used in body cells except liver.
Inhibited by G6P build-up.
Low Km.
High affinity for glucose.
More efficient.

Question 12

Regulating enzymes - Pyruvate kinase (1)

Answer 12

Inhibited by ATP - makes sense as it regulates a pathway preventing too much ATP from being produced.

Question 13

In the muscle glycolysis is required to meet the need of ATP (7)

Answer 13

ATP produces energy for contraction.
Short term.
ADPs produced from ATP can be joined.
ADP + ADP –> ATP + AMP. (Adenylate cyclase).

Cell uses ratio of ATP:AMP as an indicator of energy levels.
AMP builds up when the cell is short of energy.
ATP regulates activity of PFK
-> Lowers affinity for F6P.
-> Low pH (H+ ions) produced by lactate build up in muscles.

Question 14

Muscle cells and respiration (7)

Answer 14

Energy demand met through anaerobic respiration.
Glycolytic pathway is oxygen independent - anaerboic respiration -produces ATP in low O2 environments.
Krebs/ETC both aerobic respiration.
Muscles can work in short fast burst exertions e.g. sprints.
In normal cell glucose –> pyruvate will occur for a short period of time as NAD+ availability will decrease and ATP will inhibit PFK.

So muscle cells generate lactate which allows pathway to continue as NADH –> NAD+ which can then be fed back to earlier reaction which enables more molecules to undergo glycolysis.
Muscle can’t cope with large amount of lactate so it is exported to liver via blood.

Question 15

Why do tumours use glycolysis? (5)

Answer 15

Fast growing tumour tissue will grow faster than a blood supply can form arround it so rapid metabolism exceeds ability of blood supply to provide O2, so tumour cell metabolism switches to glycolytic processes (glycolysis).
Tumour cells not sensitive to lactate so process can continue.

Reduction in O2 leads to activation of TF HIF-1a (Hypoxia-inducible factor 1-alpha).
HIF-1a activates genes for certain enzyme in glycolytic pathway.
It moves metabolism more to the glycolytic pathway,

Question 16

Proteins in glucose metabolism encoded by genes regulated in hypoxia (oxygen deficiency)-inducible factor? (3)

Answer 16

GLUT1/3
Hexokinase
Phosphofructokinase (PFK)
Aldolase
Pyruvate Kinase
Lactate dehydrogenase
Enolase
Phosphoglycerate kinase
Glyceraldehyde-3-phosphate dehydrogenase