ML10: Fatty acids and fed & starved states

Question 1

How are fats stored in the body?

Answer 1

As triacylglycerols

Question 2

Give an overview of triacylglycerols

Answer 2

• Hydrophobic
• Stored in an anhydrous form
• Stored in specialised tissue (adipose tissue, made of adipocytes)
• Utilised in prolonged exercise, in between meals/starvation and during pregnancy
• Storage/mobilisation under hormonal and neurotransmitter control so only released when required

Question 3

Give an overview of the synthesis of fatty acids.

Answer 3

• Occurs in the cytoplasm of cells in the liver and adipose tissue
• Growing fatty acid cycles through a sequence of reactions, adding 2C each time using acetyl-CoA
• Consumes NADPH and ATP so is an anabolic process
• All intermediates linked to acyl carrier protein (ACP)

Question 4

What are the steps of fatty acid synthesis?

Answer 4

• Carboxylation of acetyl-CoA to form malonyl-CoA
  
  • ​This is a key regulated step in fatty acid synthesis
  • In the short term there is allosteric activation by citrate and inhibition by the products of fatty acid synthesis:
    
    • Phosphorylation – glucagon inhibits
    • Dephosphorylation– insulin activates
• Fatty acid synthase
  
  • ​This is a multi-functional enzyme complex
  • A cyclic process that is always coupled to a carrier protein
• Elongation and desaturation
  
  • ​C₁₆ is the usual end-point of farry acid synthase (palmitate)
  • Longer fatty acids are generated by the addition of further C₂ units in the SER
  • Desaturates in the SER are also responsible for the addition of double bonds

Question 5

How are TAGs mobilised from adipose?

Answer 5

Hormone-sensitive lipase converts. TAGs to 3 x fatty acid and glycerol

A low insulin:high glucagon ratio in the blood, controlled by the insulin:glucagon ratio, means fatty acids and glycerol diffuse into the blood

Low insulin = low blood glucose = release energy stores = breakdown of TAGs

Question 6

Compare the following characteristics of the synthesis and oxidation of fatty acids:

• Greatest flux through pathway
• Hormonal state favouring pathway
• Major tissue site
• Subcellular location
• Carriers of acyl/acetyl groups between mitochondria and cytosol
• Phosphopantetheine-containing active carriers
• Oxidation/reduction coenzymes
• 2C donor/product
• Activator
• Inhibitor
• Product of pathway
• Repetitive four-step process

Answer 6

Question 7

When are ketone bodies important?

Answer 7

When in a fasting state/starvation

Question 8

How are ketone bodies used as an alternative fuel for cells?

Answer 8

They can be converted to acetoacetyl-CoA and then to 3-hydroxy-3-methyl-glutaryl-CoA and then to acetoacetate and then to D-3-hydroxybutyrate and acetone

Acetoacetate and D-3-hydroxybuturate are used as an energy source after a couple of days of fasting

Question 9

What is the fed state? What are its characteristics?

Answer 9

• Shortly after feeding (1-2 hours)
• Fuel moelcules in abundance
• Blood glucose concentration is high
• CHO used as energy, excess converted to glycogen (liver and skeletal muscle) and TAG stores (adipose)
• Lipid used as energy and/or synthesis of membranes, excess converted to TAG stores (adipose)
• Protein used to make new proteins; some catabolised to produce energy or converted into glycogen/TAG stores

Question 10

What is the fasted state? What are its characteristics?

Answer 10

• Several hours after a meal
• Blood glucose falling (insulin was released to promote uptake of glucose)
• Insulin levels starting to fall
• Liver glycogen broken down to maintain blood glucose
• TAG stores mobilised to release fatty acids and glycerol
• Some protein catabolised to produce energy (not as significant)