Integration of Metabolism

Question 1

Ketone Body Synthesis

Answer 1

• 2 acetyl CoA combine

- final products are acetoacetate, acetone, B-hydroxybutyrate

Question 2

Ketone Body Degradation

Answer 2

• oxidation of ketone bodies back to acetyl CoA

- goes back into the TCA cycle and ATP

Question 3

Ketogenesis

Answer 3

• for B-oxidation of FA you need OA (1 per acetyl CoA in the TCA cycle)
• when fats are being oxidised, carbs are low, meaning some OA is used for gluconeogenesis
• there is not enough for all the acetyl CoA to enter the TCA cycle
• some acetyl CoA used to make ketone bodies as an alternative fuel source in tissues/synthesis in liver
• ketone bodies are made are fuel sources in starvation

Question 4

Synthesis of Glucose by Acetyl CoA

Answer 4

• only plants can do this
• isocitrate lyase: converts isocitrate into glyoxalate and succinate
• malate synthase: forms malate for use in TCA cycle using acetyl CoA
• this is the glyoxalate cycle
• net synthesis of one OA

Question 5

Cholesterol Synthesis

Answer 5

• synthesized from acetyl CoA

- committed step is the formation of mevalonate using HMG-CoA reductase and NADPH

Question 6

Key Junctions in Metabolism

Answer 6

1. G6P
   - glucose, G1P, F6P, pentose phosphate
2. Pyruvate
   - transamination with alanine, lactate conversion with carboxylase, OA and gluconeogenesis, G6P formation
3. Acetyl CoA
   - HMG-CoA used to make ketone bodies and cholesterol, oxidation in TCA cycle to make CO2, synthesis or B-oxidation of FA, also involved in amino acids

Question 7

Effect of Glucagon on Blood Glucose

Answer 7

Increases Glycogen breakdown
- activates glycogen phosphorylase
Decreases Glycogen synthesis
- inactivates glycogen synthase
Decreases Glycolysis
- inactivates phosphofructokinase 1
Increases Gluconeogenesis
- activates F 1,6 BPase
- inactivates pyruvate kinase
FA mobilization
- activates triacylglycerol lipase

Question 8

Effect of Insulin on Blood Glucose

Answer 8

Increases glucose uptake in muscle
- activates glucose transport
Increases glucose uptake in liver
- activates glucokinase
Increases glucose synthesis
- activates glycogen synthase
Decreases Glycogen breakdown
- inactivates glycogen phosphorylase
Increases FA synthesis
- activates acetyl CoA carboxylase
Increases triacylglycerol synthesis
- activates lipoprotein lipase
Increases glycolysis, acetyl CoA
- activates PFK 1
- activates pyruvate dehydrogenase

Question 9

Metabolic Labelling`

Answer 9

• radioactive labelling and detection to follow fate of compounds
• eg. 14-C
• can be universally labelled or labelled on only one specific atom/position