The Liver and Gluconeogenesis

Question 1

What is the physiological circulating blood glucose concentration?

Answer 1

3.9-6.2mM

Question 2

What is the average fasting blood glucose concentration?

Answer 2

4.4-5.0 mM

Question 3

What happens if your blood glucose levels drop below 2.5mM?

Answer 3

Coma and death

Question 4

What happens if your blood glucose levels rise above 6.2mM?

Answer 4

Dehydration, wastage of body tissue > death

Question 5

Give 3 advantages of glucose as a metabolic fuel.

Answer 5

1. Water soluble - does not require a carrier molecule in circulation.
2. Can cross the blood-brain barrier
3. Can be oxidised anaerobically - e.g. in erythrocytes.

Question 6

Give 3 disadvantages of glucose as a metabolic fuel.

Answer 6

1. Relatively low yield of ATP/mole compared to fatty acids.
2. Osmotically active so cannot be stored easily.
3. High concentrations can directly damage cells or lead to accumulation of toxic products.

Question 7

What is gluconeogensis?

Answer 7

Process of glucose generation from non-glucose sources.

Question 8

Give 3 sources of blood glucose.

Answer 8

1. Dietary glucose
2. Liver glycogen - glycogenolysis
3. Gluconeogensis - from fat and glucogenic amino acids

Question 9

When does gluconeogensis occur?

Answer 9

During carbohydrate deprivation

Question 10

Give the 3 irreversible reactions in glycolysis.

Answer 10

Hexokinase/glucokinase (converts glucose to glucose-6-phosphate)
Phosphofructokinase (converts fructose-6-phosphate to fructose-1,6-bisphosphate)
Pyruvate kinase (converts phosphoenol pyruvate to pyruvate)

Question 11

How are the 3 irreversible reactions over come in gluconeogensis to regenerate glucose?

Answer 11

Pyruvate carboxylase and PEP carboxkinase convert pyruvate to phosphoenolpyruvate.

Fructose-1,6-bisphosphatase converts fructose-1,6-bisphosphate back to fructose-6-phosphate.

Glucose-6-phosphatase converts glucose-6-phosphate back to glucose.

Question 12

How is gluconeogensis regulated?

Answer 12

Mobilisation of substrate.

Activation of enzymes by glucagon. (pyruvate carboxylase is activated by acetyl CoA)

Question 13

What happens in gluconeogensis at the muscle?

Answer 13

Alanine and lactate are released in anaerobic respiration and converted to pyruvate.

Question 14

Name the main two hormones which regulate blood glucose and control gluconeogensis.

Answer 14

Insulin (produced by beta-cells in the Islets of Langerhans)

Glucagon (produced by alpha-cells in the Islets of Langerhans)

Question 15

What is insulin?

Answer 15

An anabolic hormone - promotes synthesis and storage

Secreted by beta-cells in the Islets of Langerhans in the pancreas.

Question 16

What is the function of insulin?

Answer 16

To decrease blood glucose concentration.

Question 17

How does insulin lower blood glucose levels?

Answer 17

Inhibits gluconeogensis.
Activates glycogen synthesis in muscle and liver.
Activates fatty acid synthesis.

Question 18

What is the difference between GLUT1,2,3,4 transporters? Where are they found?

Answer 18

GLUT1 found on erythrocytes.
GLUT2 found on liver cells.
GLUT3 mainly found on brain cells.
GLUT4 found on muscle cells.

GLUT1 and GLUT3 have higher affinity for glucose - hence brain and erythrocyte are priority organs as they can only use glucose as a source of fuel.
GLUT2 has a lower affinity and is NON-insulin dependent.
GLUT4 has a lower affinity and is insulin-dependent (glucose will only enter muscle cells when insulin is present)

Question 19

What is glucagon?

Answer 19

Catabolic hormone

Promotes degradation of stored fuel

Question 20

What is the function of glucagon?

Answer 20

To increase blood glucose levels.

Question 21

How does glucagon increase blood glucose levels?

Answer 21

Increases glycogenolysis and gluconeogensis.
Increases circulating fatty acids and ketone bodies.
Increases apidose tissue lipolysis and fatty acid oxidation.