Metabolism (M2 11/12)

Question 1

The major source of energy for the brain after a prolonged fast

A)3-hydroxybutyrate

B)Acetoacetate

C)Acetone

D)Glucose

E)Fatty acids

Answer 1

A)3-hydroxybutyrate

Question 2

The pathway that generated blood glucose during a prolonged fast

A)B-oxidation

B)Glycogenesis

C)Glycogenolysis

D)Glycolysis

E)Gluconeogenesis

Answer 2

E)Gluconeogenesis

Question 3

A substrate of gluconeogenesis

A)Acetyl CoA

B)Dihydroxyacetone phosphate (DHAP)

C)Fructose 2,6 bisphosphate

D)Oxaloacetate

E)Pyruvate dehydrogenase

Answer 3

D)Oxaloacetate

Question 4

What does fructose 2,6 bisphosphate control?

Answer 4

• Controls the activity of phosphofructokinase 1.
• When lots of fructose 2,6 bisphosphate is around it activates glycolysis.
• When there is low fructose 2,6 bisphosphate gluconeogenesis is activated.

Question 5

Select a situation in the liver and adipocytes when excess acetyl CoA is converted to FAs

A)After 8 days of fasting

B)After a carbohydrate rich meal

C)Following oxidation of FAs released from adipocyte

D)After prolonged starvation

Answer 5

B)After a carbohydrate rich meal

Question 6

Select a factor that will increase the rate of gluconeogenesis in the liver#

A)Increase insulin

B)Decrease in liver fructose 2,6 bisphosphate

C)Increase on PFK1 activity

D)Decrease in glucagon

E)Decreased expression of phosphoenol pyruvate kinase

Answer 6

B)Decrease in liver fructose 2,6 bisphosphate

Question 7

How are fatty acids synthesised?

Answer 7

• FA are made when there is an excess of Acetyl CoA from carbohydrate metabolism. The Acetyl CoA is made in the mitochondria, and has to be moved to the liver or adipocyte cytosol.
• First the Acetly CoA (2 carbon) is carboxylated into Malonyl CoA (3 carbon). This uses the enzyme Acetyl CoA Carboxylase.
  
  • This enzyme is only activated when insulin or citrate levels are high (indicates excess energy).
  • It is inhibited by FA, as that is the end product.
• To form FA there are 7 reactions, all catalysed by Fatty Acid Synthase in cytosol:
  
  • What happens is a Malonyl CoA and Acetly CoA combine to add two carbons to the Acetyl CoA each time they react together. (The missing carbon forms CO2)
  • This is an anabolic process. Each time two carbons are added, 2xNADPH is converted into NADP+, CO2 and 2XCoA
• The main product of FA synthesis is a 16 carbon fatty acid called Palmitate.

Question 8

How are TAGs broken down during a fast?

Answer 8

1. They are hydrolysed into 3 FA and glycerol by Hormone Sensitive Lipase in the adipocytes.
2. HSL is activated by high glucagon, epinephrine (adrenaline) and norepinephrine.
3. The glycerol is transported to the liver for gluconeogenesis.
4. The FA’s are released into blood, the bind to albumin and enter cells.
5. In liver FA’s are used to make ketone bodies. In all other tissues, except the brain FA’s are beta oxidised to Acetyl CoA, ehich then enters the Krebs cycle.

Question 9

What are the different length fatty acids classified as?

Answer 9

• Small Chain FA: less than 6 carbons
• Medium Chain FA: between 6-11 carbons
• Long Chain FA: between 12-22 carbons
• Very Long Chain FA: more than 22 carbons

Question 10

Describe Beta Oxidation of FAs

Answer 10

• In all tissues apart from the brain beta oxidation can happen, because in the brain FA’s can’t pass the blood brain barrier.
• In all tisssues apart from the liver, beta oxidation is used to make Acetyl CoA to enter the krebs cycle to make energy. In the liver beta oxidation of fatty acids is used to make ketone bodies for the brain instead.
• When a FA enters a cell, it has to be acylated before it can pass through the mitochondrial membrane. The fatty acid is now fatty AcylCoA.
• Small and MC fatty AcylCoA can diffuse through the mitochondrial membrane.
• LC fatty AcylCoA use the ‘carnitine shuttle’ to get into the mitochondria.
• VLC fatty AcylCoA have to be degraded by peroxisomes.
• Beta Oxidation of fatty AcylCoA happens in the matrix AKA the cytoplasm of the mitochondria. There are 4 reactions in beta oxidation.
• Each time beta oxidation happens one FADH2 and NADH is made, and an acetly CoA is made (used for ketogenesis in the liver, or krebs in other tissue).
• 1 Palmitoyl CoA can make 131 ATP.

Question 11

In each cycle of Beta Oxidation two carbons are removed. Each cycle requires 4 recations catalysed by which four enzymes?

Answer 11

1. Acyl CoA dehydrogenase (four different types because it is length specific: VLC, LC, MC, SC)
2. Enoyl CoA dehydrogenase
3. 3 Hydroxyacyl-CoA dehydrogenase
4. β-Ketoacyl-CoA thiolase