Lecture 5 - Introduction to Metabolism - Glycolysis II

Question 1

glucose carrier composition:

Answer 1

glucose carriers consist of a protein chain that crosses the membrane about 12 times and has at least 2 conformations - switch back and fourth

one conformation exposes the binding site to the outside of the cell and the other to the inside of the cell

Question 2

human erythrocytes structure and how it alters theor form of ATP production:

Answer 2

•No mitochondria (no nucleus, and no other cellular organelles)

•Require ATP for Na+/K+ ATPase pump in keeping membrane potential which contributes to the maintenance of biconcave shape

•Relying entirely on glycolysis for ATP

•Glycolysis in the cytosol is the sole source of ATP

Question 3

what are the different types of glucose transporters?

Answer 3

GLUT 1, GLUT 2, GLUT 3, GLUT 4

Question 4

where is GLUT 1 found and describe its affinity:

Answer 4

GLUT 1 is found primarily in erythrocytes and other tissues with a high affinity (~ 1 mol/L)

Question 5

where is GLUT 2 found and describe its affinity:

Answer 5

GLUT 2 is found in the liver and pancreatic B cells - these glucose carriers have the lowest affinity for glucose (~ 15mmol/L)

Question 6

where is GLUT 3 found and describe its affinity:

Answer 6

GLUT 3 is found in the brain and other tissues, this glucose carrier has a high affinity for glucose (~1 mol/L)

Question 7

where is GLUT 4 found and describe its affinity:

Answer 7

GLUT 4 is found in the muscles and adipose tissue and this glucose carrier has a low affinity of (~ 5mmol/L)

Question 8

hexokinase is allosterically inhibited by high levels of ______, this is an important control step because:

Answer 8

it prevents over consumption of cellular ATP to form G-6-P when glucose is not limiting

Question 9

what glucose concentrations are hepatocytes exposed to?

Answer 9

regularly exposed to relatively high glucose concentration via hepatic portal vein

Question 10

what glucose carrier protein do hepatocytes express:

Answer 10

expresses GLUT 2 that has the highest Km that shows the lowest affinity to glucose

Question 11

what do hepatocytes use instead of hexokinase for the phosphorylation of glucose and how do the Km values differ between the two enzymes?

Answer 11

• Expresses Glucokinase (GK) instead of Hexokinase (HK) for the phosphorylation of glucose
• GKs have higher Km than HK those show relatively low affinity to glucose

Question 12

difference in inhibition between HK & GK:

Answer 12

Gk high Km; is activated by high blood glucose and insulin but NOT inhibited by G-6-P like Hk is

Question 13

what does Gk allow for and why is it so crucial?

Answer 13

enzyme allows the liver to remove excess glucose for glycogen synthesis and minimise, after eating, hyperglycaemia

Question 14

2 primary isoforms (isozymes) of pyruvate kinase and their locations:

Answer 14

• M-type: Muscle & Brain
• L-type: Liver

Question 15

L-type pyruvate kinase is covalently phosphorylated when:

Answer 15

blood glucose is low

Question 16

Phosphorylated L-type is less active compared to … which prevents:

Answer 16

those not phosphorylated

this prevents liver cells to consume glucose when there is a demand in other parts of the body

Question 17

cori cycle:

Answer 17

in an oxygen deficit anaerobic respiration, muscle cells produce lactate. In the Cori cycle, lactate is released in the blood. In the liver conversion of lactate to pyruvate and to glucose takes place using 6 ATP by a process known as gluconeogenesis. Glucose is then released from liver cells back into the blood to be taken up by peripheral tissues.

Question 18

summary of gluconeogenesis:

Answer 18

•Takes place primarily in the liver and kidney cells

•Essential for maintaining blood glucose concentration

•Major precursors are Glycerol, amino acids, and lactic acid

•Require specific enzymes (it is not a reverse of glycolysis)

Question 19

The energy conserving phase of glycolysis generates:

Answer 19

2xNADH and 2xATP from glucose

Question 20

Pyruvate kinase is a key regulatory step, modulated by:

Answer 20

hormones, ATP and fructose 1,6-bisphosphate

Question 21

Pyruvate used to make ATP in anaerobic conditions generates:

Answer 21

lactate which is recycled in the liver using the Cori cycle

Question 22

Pyruvate dehydrogenase is another key enzyme regulated by:

Answer 22

energy and acetyl CoA

Question 23

glycolysis yields:

Answer 23

Yields 2 ATP (net total) molecules for every one glycose molecule digested down to pyruvate

➢Yields 2 NADH per every glucose digested by glycolysis

Question 24

glycolysis takes place in:

Answer 24

the cytosol

Question 25

glycolysis - ana/aerobic?

Answer 25

anaerobic

Question 26

Hypoxia-inducible factor (HIF) regulated genes:

Answer 26

oxygen deprived, hypoxia is known to allow HIF transcription factor to turn on many enzymes of glycolysis

Question 27

gluconeogenesis - 2 carboxylates to regenerate:

Answer 27

Phosphoenolpyruvate

Question 28

gluconeogenesis - Glycerol as substrate to regenerate:

Answer 28

DHAP

Question 29

4 key enzymes of gluconeogenesis:

Answer 29

hexokinase - Glucose
6-phosphatase

phosphofructokinase - Fructose
1,6-bisphosphatase

pyruvate kinase - Phosphoenol- pyruvate carboxylase & Pyruvate carboxylase

Question 30

Warburg Effect:

Answer 30

tumours and other proliferating or developing cells, the rate of glucose uptake dramatically increases and lactate is produced, even in the presence of oxygen and fully functioning mitochondria

Question 31

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