Lecture 32: Coordinating metabolism - fuel storage

Question 1

Why do we need fuel stores?

Answer 1

After a meal there is an excess of fuel, so the excess is stored

Fuel stores are crucial for maintaining energy balance, providing a buffer for periods of low food intake, supporting physical activity, and enabling the body to adapt to changing energy needs and conditions.

Question 2

Can we directly store ATP or transfer it to different tissues?

Answer 2

We can’t store ATP or transfer it to other tissues, it must be made in the cell requiring it at the time by oxidizing fuels

Question 3

What constitutes the biggest fuel store for energy?

Answer 3

Adipose tissue (fat) constitutes to the biggest fuel store for energy in the body

Question 4

Describe how insulin promotes fat synthesis.

Answer 4

• Excess glucose carbon can be converted to
  fatty acids via acetyl-coA as a result of insulin stimulated uptake - Occurs mainly in liver but also in adipose
• Energy-requiring process
• FAs exported as TAGs in VLDL
• FAs delivered to adipose via LPL activity (lipoprotein lipase which hydrolyses TAGs to release FA into tissues where they are resynthesized into TAGs and stored
• Overall process Stimulated by insulin

Question 5

How does excess glucose get converted to fat?

Answer 5

Glucose provides glycerol-phosphate backbone and provides acetyl-coA for de novo lipogenesis (DNL) (fat generation)

Question 6

Where is glycogen stored?

Answer 6

• Stored in liver and muscle
• Granules in cytoplasm

Question 7

What is glycogen and what bonds does it have?

Answer 7

• Branched polysaccharide
• A,1-4 and A,1-6 glycosidic bonds

Question 8

Which glycogen store can maintain blood glucose levels?

Answer 8

The glycogen stored in the liver can maintain blood glucose levels for long periods in between meals

Question 9

Name a key enzyme for glycogen synthesis and describe the reaction it catalyses.

Answer 9

Glycogen synthase

The enzymes helps release the UDP from UDP-Glucose which allows the now free glucose molecule (oxonium ion intermediate) to bind to the growing Glycogen unit forming a new glycosidic bond

Question 10

Define what a glycogen storage disease is.

Answer 10

Inherited metabolic disorders involving a deficiency of one of the enzymes responsible for glycogen synthesis or breakdown.

Leads to an abnormal accumulation or deficiency of glycogen in liver or muscles

Symptoms include hypoglycemia, ketosis, muscle cramps and fatigue, enlarged liver (hepatomegaly), growth retardation in children.

Question 11

Can muscle glycogen be mobilised to serve other tissues?

Answer 11

NO

Muscle glycogen can only be used within muscle as muscle cells are missing glucose-6 phosphatase which can break down Glucose-6-Phosphate back into glucose to be released into the blood stream

Question 12

What kind of bond does Glycogen Synthase create and what type of bond does the branching enzyme for glycogen create?

Answer 12

Glycogen synthase forms A 1-4 Glycosidic bonds between glucose units

The branching enzyme forms A 1-6 Glycosidic bonds between the main chain of glycogen and the growing sidechains

Question 13

Describe the overall process of glycogen synthesis:

Answer 13

• Occurs mainly in liver and muscle immediately after a meal
• Requires energy inputs (ATP and UTP)
• Activated high-energy precursor, UDP-glucose
• Glycogen synthase and branching enzyme
• Stimulated by insulin

Question 14

How does insulin promote glycogen synthesis?

Answer 14

Stimulation of the insulin signalling pathway activates PKB (aka AKT) which inactivates glycogen synthase kinase (GSK3)

Inactivation of GSK3 prevents glycogen synthase from being phosphorylated which keeps it active

Insulin also activates a phosphatase (PP1) which dephosphorylates glycogen synthase, which also keeps it active