Lecture 34 - Lipid synthesis and degradation

Question 1

Fats play an essential role in biological functions (4)

Answer 1

Membranes
Uptake of lipid soluble vitamins
As precursors of sterois hormones
Energy store

Question 2

Energy content in 1 g of Fat, Protein, Carbohydrate (3)

Answer 2

Fat = 37 kJ
Protein = 17 kJ
Carbohydrate = 16 kJ

Question 3

Health implications (6)

Answer 3

40% of the energy from british diet is from fat.
Obesity rose from 14.9% to 25.6% between 1993 and 2014 in England classifed obese.
75% of population will be obese in 15 years.
In 2016: 62.8% of adults and 30.3% of children were overweight/obese.
26.1% of all adults and 16% of all children were obese.

Question 4

Fatty acids (5)

Answer 4

• Chains of methyl groups.
• Terminal carboxyl group.
• Double bonds if present are usually in cis conformation.
• Humans unable to create double bonds less than position 9.
• Essential fatty acids obtained from the diet.

Question 5

Fatty acid synthesis - Overview (6)

Answer 5

Cytosol.
Requires: Acetyl-CoA, NADPH, ATP.
It involves the sequential addition of 2 two carbon units derived from acetyl-CoA.
Intermediates linked to acyl-carrier protein.
Reductant NADPH.
Fatty acid synthase enzyme complex.

Question 6

Fatty acid synthesis - Transfer of ACoA to the cytosol (6)

Answer 6

Citrate is formed in the mitochondria.
Transported into cytosol via citrate-malate antiport.
In the cytosol citrate breaks down into ACoA and oxaloacetate.
Oxaloacetate –> Malate –> Pyruvate (producing NADPH, used for FA synthesis).
Pyruvate transported back into the mitochondrion, converted back into oxaloacetate.
Cyclical process.

Question 7

Fatty acid synthesis - STEP1/2

Recreate diagram

Answer 7

Drawn on sheet

Question 8

Cholesterol - Overview (5)

Answer 8

Rigid hydrophobic molecule.
Insoluble in water.
Precursor of sterols, steroids and bile salts.
NOT an energy forming molecule - can’t be oxidised to O2 or H2O.
Transported in circulation as cholesteryl esters.

Question 9

Cholesterol synthesis (6)

Answer 9

Synthesised mostly in ER, over 30 steps.
Starts with activation of acetate to acetyl-CoA.
You can generate cholesterol from a carbohydrate source.
Major regulatory step: Conversion of HMGCoA to mevalonate by HMGCoA reductase.
Cholesterol inhibits HMGCoA reductase (enzyme involved in its own synthesis - it is self regulating) -difficult to reduce circulating cholesterol by diet alone, as ENDOGENOUS SYNTHESIS is increased.
So it needs to be tackled by inhibiting this enzyme and diet.

Question 10

Fatty acid degradation - Overview (7)

Answer 10

Release of energy from reserves stored in adipose tissue requires three steps.
Important when food is not readily available i.e. starvation or exercise stimulated by glucagon and andrenaline but inhibited by insulin.
Mitochondria.
Intermediates linked to coenzyme-A.
Sequential removal 2C.
Oxidants FAD and NAD.
Carried out by individual enzymes.

Question 11

Fatty acid degradation - STEP 1/2/3 On sheet

Answer 11

On sheet

Question 12

Ketogenesis - On sheet

Answer 12

On sheet

Question 13

Ketogenesis - Fate of ketone bodies (2)

Answer 13

Major energy source for cardiac muscle and renal cortex
- dependent on the flow of carbohydrate in glycolysis.

During starvation up to 75% of the brains energy is derived from acetoacetate.

Question 14

Hormonal Regulation of Fat Metabolism - Insulin (4)

Answer 14

↑ glycolysis in the liver
↑ Fatty acid synthesis in the liver
↑ TG in adipose tissue
↓ b-oxidation

Question 15

Hormonal Regulation of Fat Metabolism - Glucagon and adrenaline (1)

Answer 15

↑ TG mobilisation