MCBG Session 7 - Lipids

Question 1

Are lipids hydrophilic or phobic?
What do they mostly contain?
Are they more or less reduced than carbohydrates?

Answer 1

• Hydrophobic
• Mainly contain C,H&O (phospholipids also contain P & N)
• More reduced than carbohydrates so release more energy when oxidised.

Question 2

Describe the 3 classes of lipids and give examples of each.

Answer 2

1) Fatty acid derivatives - e.g.: fatty acids, triglycerides & phospholipids
2) Hydroxy-methyl-glutaric acid derivatives - which can form ketone bodies, cholesterol and bile salts
3) Vitamins - e.g.: A,D,E & K.

Question 3

How much weight in a healthy 70kg male is comprised of triglycerides?

Answer 3

• 15kg (600,000 kJ energy content).

Question 4

Describe the structure, storage & function of triacylglycerols (TAG’s)/triglycerides.

Answer 4

• Structure = 3C glycerol backbone, with fatty acid side chain attached to each C. They join together via esterification reaction (removal of water).
• Storage = Hydrophobic so stored in anhydrous form in adipose tissue.
• Function = utilised during prolonged exercise, starvation or pregnancy - under hormonal control.

Question 5

Describe where and how TAG’s are metabolised.

Answer 5

1) TAG’s are first metabolised extracellularly in the GIT into fatty acids and glycerol by pancreatic lipases.
2) fatty acids and glycerol are recombined in the small intestine and transported as TAG by lipoproteins (chylomicrons).
3) They are either taken to consumer tissues and oxidised to provide energy or stored in adipose tissue..
4) An increase in glucagon/adrenaline or a decrease in insulin causes mobilisation of TAG’s from adipose tissue to consumer tissues.

Question 6

What do low extracellular glucose levels result in the release of?

Answer 6

Fatty acids as an alternative fuel source. This is because the levels of glucose required to become glycerol-1P to combine with fatty acyl-CoA to reform TAG form decrease, therefore fatty acids build up and are released.

Question 7

What 3 types of fatty acids can you get? (based on structure)

Answer 7

1) Saturated
2) Unsaturated (one or more double bonds)
3) Amphipathic (contain hydrophilic and phobic groups)

NB - certain polyunsaturated FA’s are essential as mammals cannot introduce double bond at C9, e.g.: linolenic acid.

Question 8

Where does fatty acid catabolism occur and describe the 3 main steps involved.

Answer 8

• It occurs in the mitochondria
  1) FA’s are activated by linking to CoA via fatty acyl CoA synthase.
  2) Activated FA’s cannot cross inner mitochondrial membrane so pass using the carnitine shuttle
  3) FA goes through sequence of oxidative reactions removing 2C’s each cycle (also produced NADH/FADH)

Question 9

From which is more energy derived - oxidation of fatty acids or glucose?

Answer 9

Fatty acids. (41 moles ATP compared to 32 from glucose).

Question 10

How and where is glycerol metabolised?

Answer 10

Glycerol is transported in the blood to the liver where its metabolised:

• Glycerol to glycerol phosphate via glycerol kinase
• Can either be used in TAG synthesis or to produce DHAP for glycolysis.

Question 11

What are the constituents and bonds in Acetyl-CoA (main convergence point for catabolic pathways)?

Answer 11

• Acetate and CoA linked via S-atom - which has high energy of hydrolysis.

Question 12

What are the 3 ketone bodies produced in the body?

What are normal, starvation and untreated type 1 diabetes ketone body concentrations?

Answer 12

• Acetoacetate, Acetone & B-hydroxybutyrate
• Normal = >1mM
• Starvation = 2-10mM (physiological ketosis)
• Untreated T1 diabetes = >10mM (pathological ketosis)

Question 13

Where and how are ketone bodies synthesised?

Answer 13

• In the liver mitochondria
• AcetylCoA to HMG-CoA via synthase
• HMG-CoA can either be converted to mevalonate (and eventually cholesterol) via HMG-CoA reductase or acetoacetate via lyase (ketone body synthesis).

Question 14

How is the production of ketone bodies regulated?

Answer 14

Regulated via the fed state, e.g.:

• When insulin/glucagon ratio is high (fed state) - lyase is inhibited, reductase is activate to form mevalonate and ultimately cholesterol.
• When insulin/glucagon ratio is low (starvation state) lyase is activated, reductase is inhibited leading to ketone body synthesis

Question 15

What is the role of ketone bodies in early starvation/diabetes?

Answer 15

To spare/save glucose by providing muscle with energy in order to allow circulating glucose to provide fuel to the brain which is prioritised.

Question 16

Describe the characteristics of ketone bodies.

Answer 16

• Water soluble
• Permits high plasma concentrations
• Above renal threshold = excreted in urine (ketonuria)
• Acetoacetate and B-hydroxybutyrate are strong organic acids (can cause ketacidosis)
• Volatile acetone excreted via lungs - gives strong nail varnish like smell.