Glycolysis

Question 1

How can ATP be produced ?

Answer 1

Oxidation through aerobic glycolysis yields pyruvate - efficient
Fermentation by anaerobic glycolysis yields lactate - rapid, inefficient

There is oxidation of glucose by NAD+ during glycolysis

Question 2

What are the roles of glucose ?

Answer 2

ATP production and providing the building blocks for synthetic reactiond

Question 3

How does glucose provide the building blocks for synthetic reactions ?

Answer 3

Oxidation through pentose phosphate pathway → ribose-5-phosphate
-This is the recursor for nucleotide synthesis and DNA repair → growth

Question 4

What happens in the absense of oxygen ?

Answer 4

Anaerobic metabolism
1) Pyruvate can act as a hydrogen acceptor, taking hydrogen ions from NADH
2) Pyruvate is converted into lactate and NAD is regenerated

Pyruvate + NADH + H+ = lactate + NAD+, H- from NADH

Question 5

What supports the Warburg effect in cancer cells ?

Answer 5

Cancer cells have low Km hexokinase
-Supports rapid cell growth - energy production, pathways for nucleotide synthesis
-Produces H+ and lactate as end products
-Inefficient ATP synthesis with high glucose demand

Question 6

What is anabolism and catabolism ?

Answer 6

Anabolism
-Building stuff, requires energy, reductive

Catabolism
-Breaking stuff, produces energy, oxidative

Question 7

What is glucose eventually oxidised to ?

Answer 7

Full oxidation of glucose produces C02 and H20

Question 8

Which organ loves yummy yummy glucose the most

Answer 8

Greedy Brain
-Accounts for 20% of glucose use but only 2% of body weight
-If blood sugar drops, brain sees symptoms first; many neurological issues related to metabolism

Question 9

Which bond in ATP is of the highest enery

Answer 9

This one

Question 10

What is glucotoxicity ?

Answer 10

Mammalian cells/tissue cannot tolerate chronic hyperglycemia
-Glucose toxic at high conc
-Ketoacidosis and if chronic, micro/macrovascular disease
-Diabetes issues

Glucose stored as an inert polysaccharide, glycogen
-In liver, muscle, brain

Question 11

What are the four fates of glucose ?

Answer 11

Glycolysis to produce pyruvate then oxidation
-Efficient ATP Production by oxidative metabolism
-Involves oxidative phosphorylation after glycolysis

Glycolysis to produce pyruvate then fermentation
-Occurs when no oxygen
-Produces lactate
-Rapid, ineffeicient ATP production

Oxidation through Pentose Phosphate Pathway
-Produces Ribose-5-phosphate, a precursor for nucleotidesynthesis & DNA repair and Essential for Growth

Conversion to Glycogen or lipids for storage

Question 12

How is glucose transported into cells ?

Answer 12

Via Na+/glucose symporter
-Passive facilitated diffusion by GLUT glucose transporters
-Different GLUT transporters are found in cells of different tissues and have different Km values; low Km means transport glucose at lower concs

Km = substrate conc when reaction rate is half of max (Vmax)

Question 13

Which tissues have which glucose transporters ?

Answer 13

Brain
-GLUT 1 and 3, both low Km

Liver and pancreas beta-cells
-GLUT 2, high Km and insulin independent

Muscle and adipose tissue
-GLUT 4, Insulin-dependent

Gut
-GLUT 5 , does fructose transport

Brain is always hungry for glucose

Question 14

What is glycolysis and its steps ?

Answer 14

Glycolysis is the the initial pathway for the conversion of glucose to pyruvate

1) Glucose phosphorylation to fructose-1,6-bisphospate
-Requires energy; 2ATP to 2ADP
-Phosphofructokinase converts 6 to 1,6
2) Froctose-1,6-biphosphate to 2x triose phosphate three-carbon carbohydrates
-By aldose
3) Triose phosphate oxidation produces pruvate from each
-4ATP generated from 4ADP
-2NAD+ reduced to 2NADH and 2H+

Per glucose there is a net gain of 2ATP, 2NADH and 2H+

Question 15

Describe pyruvate kinase in controlling glycolysis

Answer 15

Controls conversion of phosphoenolpyruvate to pyruvate (product exit)

Question 16

What is the overall equation for glycolysis ?

Answer 16

Question 17

What are the control points of glycolysis ?

Answer 17

Three enzymes catalysing irreversible reactions

Hexokinase; glucose retention
Phosphofructokinase; rate of glycolysis
Pyruvate kinase; product exit

(Also glyceraldehye 3-phosphate, not an enzyme)

Question 18

Describe hexokinase inhibition control of glycolysis

Answer 18

Hexokinase catalyses glucose + ATP -> glucose-6-phosphate (G6P) + ADP
-Phosporylation of glucose traps it in cell
-High levels of G6P inhibits hexokinase; feedback inhibition
-Prevents further cell glucose retention; cell doesnt take on too much glucose
-Occurs in response to high glucose conc

High glucose conc; glycolysis producing G6P outruns oxidative phosphylation so G6P accumulates

Question 19

Describe glyceraldehye 3-phosphate in controlling glycolysis

Answer 19

Matches the rate of reaction to the rate of NADH regeneration

Question 20

Describe Phosphofructokinase activation in controlling glycolysis

Answer 20

Is a key enzyme that controls the rate of substrate movement in glycolysis (rate-limiting)
Catalyses fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis
-Activated by AMP – increases glycolysis when energy is needed

Question 21

Describe Phosphofructokinase inhibtion in controlling glycolysis

Answer 21

ATP
-Slows glycolysis if energy abundant

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

H+
-Slows glycolysis if too much lactic acid is being produced in anaeorbic respiration

These are all negative feedback

Question 22

Why is AMP the positive regulator of phosphofructokinase, and not ADP?

Answer 22

ATP rapildy used; ADP + Pi
Adenylate kinase salvages energy in ADP; 2ADP -> ATP + AMP
-This means ADP usually at quite consistent levels in cell so energy levels measured by looking at ATP and AMP

Question 23

What is energy charge ?

Answer 23

The ATP/AMP ratio
-Cell if fully “charged” if all adenylate nucleotides are ATP
-Cell is “discharged” if only contains AMP and Pi

Cell usually somwhere between fuly charged and discharged

Question 24

Where does NADH and H+ from glycolysis go ?

Answer 24

Electron transport chain for ATP synthesis

NAD+ regeneration means oxidising NADH to NAD+

Question 25

What happens to pyruvate in anaerobic respiration/fermentation ?

Answer 25

Terminal electron acceptor is normally oxygen, but here it is pyruvate -NADH gives electron to pyruvate which forms lactate -This regenerates NAD+ | NADH donating electron = gives hydride, H-

Question 26

What is the Warburg effect ?

Answer 26

Cancer cells produce energy by high rate of glucose metabolism to lactate to spam division; anaerobic glycolysis -Inefficient but quick Cancer can be treated by targeting glycolysis -patients given enzymes which act around control points | May be done due to poor tumour blood supply

Question 27

How do cancer cells get loads and loads of yummy yummy glucose ??

Answer 27

Cancer cells generally have low Km Hexokinase which increases glucose movement into the cell -Drinks glucose even when it is at low concentration -Causes weightloss

Question 28

How can products of glycolysis aid tumour growth ?

Answer 28

Produces H+ and lactate -Lactate damages tumour-infiltrating T cells and NK cells and activates immune suppressive cells