29. Lipid Synthesis & Degradation

Question 1

What are lipids?

Answer 1

Macromolecules soluble in non-polar solvents

Question 2

What are the health implications of fats? (2pts)

Answer 2

1. 40% of the energy of the British diet is from fat

2. 75% of the population will be obese within 15 years. Government policy is to reduce this to 35%.

Question 3

What are fats? (4pts)

Answer 3

1. Fats are made from dietary carbohydrates
2. Fats can also be made from Amino acids,
3. Not all fats are stored as they are also the preferred energy source for cardiac muscle.
4. Fats are stored in the adipose tissue as triglycerides but the majority are synthesized in the liver.

Question 4

Describe fatty acid features?

Answer 4

1. Chains of methyl groups with a terminal carboxyl group
2. Double bonds if present are usually in cis conformation
3. Essential fatty acids are obtained from the diet.

Question 5

Describe what happens when glucose enters the liver cell? (4pts)

Answer 5

1. Glucose enters the liver cell
2. it is phosphorylated to glucose-6-phosphate
3. The Glucose-6-phosphate is further metabolised in glycolysis to form pryuvate
4. The pyruvate is converted to Acetyl-CoA and reacts with oxaceletic acid to form citrate.

Question 6

What happens to excess citrate? (4pts)

Answer 6

1. Excess citrate is transported out of the mitochondria
2. It is converted back into Acetyl-coA
3. Acetyl-coA is synthesized into fatty acids
4. The fatty acids is retained in the liver but the majority will be transported in the blood as lipoproteins or free fatty acids to adipose sites for storage.

Question 7

What is Acetyl-coA used to synthesise?

Answer 7

Cholesterol

Question 8

Describe the transfer of acetyl coA to the cytosol? (5pts)

Answer 8

1. Acetyl coA reacts with oxaloaecetate to produce citrate
2. Citrate is transported out of the mitochodnria into the cytosol
3. The Acetyl coA is regenerated along with Oxaloacetate.
4. The Oxaloacetete is converted into malate.
5. Malate is converted to Pyruvate forming NADPH in the process.
6. Pyruvate is transported back into the mitochondria where it is converted to oxaloacetate.

Question 9

Describe the fatty acid syntesis equation? (3pts)

Answer 9

1. Acetyl-coA + ATP + HCO3- = manoly-CoA + ADP + Pi
   - important irreversible regulatory step activated by citrate and inhibited by palimitic acid.
2. Acetyl-coA combines with HC03 to form Malonly-coA
3. Malonyl-coA combines with ACP to form Malonly-ACP.

Question 10

What is the protein responsible for fatty acid synthesis?

Answer 10

Fatty acid synthase. This is a multienzyme complex that brings together the substrate and the enzyme active site.

Question 11

Summarise Fatty acid synthesis? (6pts)

Answer 11

1. Takes place in the fed state when glucose levels are high and demand for ATP is low
2. Stimulated by insulin
3. Takes place in a number of tissues but mainly in the liver.
4. Inhibited by glucagon, adrenaline and noradrenaline.
5. Fatty acids are transported as triglycerides which are the major storage molecule.
6. Fatty acids are stored by adipocytes.

Question 12

Describe Cholesterol? (6pts)

Answer 12

1. Rigid hydrophobic molecule virtually insoluble in water
2. Precursor of sterols, steroids and bile salts.
3. Important membrane components
4. Transported in the circulation as cholesterol esters
5. Cannot be used to provide energy
6. Cholesterol imbalance leads to significant health issues.

Question 13

Describe Cholesterol synthesis? (6pts)

Answer 13

1. Occurs mostly in the ER.
2. Over 30 steps involved
3. Starts with the activation of acetate, acetyl coA.
4. Major regulatory step is the conversion of 3-hydroxyl-3-methylglutayrl coA to mevalonate.
5. Cholesterol inhibits HMGCoA reductase.
6. Difficult to reduce circulating cholesterol by diet alone as endogenous synthesis is increased.

Question 14

Describe fatty acid degradation? (3pts)

Answer 14

Release of energy from reserves stores in adipose tissue requires 3 steps:

1. Mobilisation- adipoctye
2. Activation- liver cytosol
3. Degradation- liver mitochondria

Question 15

Describe Mobilisation? (3pts)

Answer 15

1. Fatty acids are transported to the liver and acitvivated by acycl-coA synthase in the cytoplasm to form acyl-coA
2. Fatty acyl-coA reacts with the alcohol carnote to form fatty acyl-carnite
3. Fatty acyl-carnite is then transported across the inner mitochodnrial membrane.

Question 16

Describe activation in the liver? (3pts)

Answer 16

1. Carnite reacts with the Acyl CoA to form Acyl carnite.
2. This is then transported across the inner mitochondrial membrane via translocase.
3. Acyl carnite is then broken down to give Carnite and Acyl CoA.

Question 17

Describe fatty acid oxidation (B-oxidation) in the liver mitochondria? (2pts)

Answer 17

1. Acyl-coA degraded by sequential removal of two carbon units.
2. As a result FADH2, NADH and acetyl-coA are produced. This will continue until fatty acid chain has been completely broken down.
3. FADH2 and NADH form ATP

• in the liver the acetyl coA does not enter the citric acid cycle

Question 18

Fatty acid degradaton summary? (7pts)

Answer 18

1. Takes place in the fasting state when glucose levels are low or when demand for ATP is high
2. Stimulated by glucagon, adrenaline and noradrenaline
3. Inhibited by insulin
4. Takes place in a number of tissues including the liver kidney and muscle
5. Takes place in the mitochihondria-b oxidation
6. In the liver the main product acetyl-coA is used for ketogenesis
7. In cardiac and skeletal muscle acetyl-coA is used to make ketogenesis.

Question 19

What is Ketogensis?

Answer 19

The production of ketone bodies

Question 20

Describe ketogensis (5pts)

Answer 20

1. Fasting, uncontrolled diabetes and prolonged exercise stimulates fatty acid breakdown producing acetyl-coA.
2. Metabolism shifts towards maintaining blood glucose leading to a reduction in OAA.
3. Loss of OAA limits energy production from acetyl-coA.
4. Excess acetyl-coA is used to form ketone bodies
5. Ketone bodies are acetoacetate, 3-B-hydroxybutrate and acetone.

Question 21

Describe how ketone bodies are formed? (4pts)

Answer 21

1. 2 molecules of Acetyl CoA combine to form Acetaoacetyl coA.
2. Acetocetyl-Co-A then combines with Acetyl CoA to form 3-hydroxy-3-methylglutaryl-coA. This is catalysed by HMG-CoA synthase enzyme.
3. HMG-CoA is then cleaved to form acetoacetate and acetyl-coA
4. The acetoacetate is then converted to acetone and 3-B-hydroxybutyrate.

Question 22

Describe the fate of ketone bodies? (2pts)

Answer 22

1. Used by cardiac muscle and renal cortex

2. Used by the brain during starvation

Question 23

Describe the fate of Glycerol? (3pts)

Answer 23

1. Breakdown of triglycerides gives acetyl-coA and glycerol
2. In the liver glycerol is used to synthesise glucose by glyocgenogensis
3. In the muscle glycerol is used in glycolysis and oxidative phosphorylation to produce ATP.

Question 24

Summarise lipid breakdown? (4pts)

Answer 24

1. Triglycerides are broken down into glycerol and fatty acids in adipocytes
2. Glycerol is fed in to glycolysis or glucogenesis.
3. In the liver free fatty acids are activated and transported to the mitochondria
4. Fatty acids are broken down in a step by step manner in to acetyl coA.

Question 25

Describe how insulin regulates fat metabolism? (4pts)

Answer 25

1. increases Glycolysis in the liver
2. increases fatty acid synthesis in the liver
3. Increases triglycerides in adipose tissue
4. Decreases beta oxidation

Question 26

Describe how glucagon and adrenaline regulates fat metabolism? (4pts)

Answer 26

Increases triglyceride mobilization