Lipid Breakdown

Question 1

List the 3 sources of energy

Answer 1

Glucose
Glycogen
Fats
All three are linked by metabolic pathways and can be interconverted
Technically proteins as well

Question 2

Overview of metabolic pathway

Answer 2

Glucose pathway to TCA pathway.
Glucose is converted to Glyceraldehyde-3-phosphate, then converted to phosphoenol pyruvate -> pyruvate -> acetyl-CoA -> TCA cycle

Glucose pathway to fats
Glyceraldehyde-3-phosphate -> glycerol -> fats -> fatty acids -> acetyl-CoA

TCA pathway to glucose
Oxaloacetate from TCA -> Phosphoenol pyruvate -> Glyceraldehyde-3-phosphate -> Glucose

Amino acids can join via 3 ways
Pyruvate, Acetyl-CoA or several components of citric acid cycle

Question 3

Fun fact about fat

Answer 3

By weight, fat has 3x the energy of glucose.

Question 4

Molecules that enter mitochondria for oxidation

Answer 4

Pyruvate from glucose metabolism and fatty acids from fatty acid metabolism is carried from cytosol to mitochondria to be converted into acetyl CoA

Question 5

Pathway of fat through the body

Answer 5

Adipose tissues where triglycerides are stored, it is converted to fatty acids via lipolysis. Fatty acids travel through blood to reach muscle cells where beta oxidation occurs to become acetyl-CoA

Question 6

Triglyceride chemical structure

Answer 6

3 fatty acids acyl groups
1 glycerol
They are linked by ester bonds and triglycerides are hydrolyzed into glycerol and fatty acids by adding 3 molecules of water

Question 7

Saturated vs Unsaturated fatty acids

Answer 7

Saturated fatty acid

• No double bond
• Straight chain, can be packed very tightly

Unsaturated fatty acid

• Consist of cis and trans double bond(s)
• Monounsaturated
• Polyunsaturated
• Trans-fat are unsaturated fatty acids with trans double bonds instead of cis double bonds
• Omega-3,6,9 are polyunsaturated fatty acids characterized by the presence of a double bond 3 atoms away from the terminal methyl group

Question 8

Lipolysis or fat breakdown

Answer 8

Glycerol breakdown will not be covered for the module
Fatty acids will be converted to acetyl-CoA, which can be become citric acid and acetoacetate. Citric acid can enter the Kreb cycle and acetoacetate can be converted to ketone bodies.

Question 9

Hormone control of lipolysis

Answer 9

Epinephrine and glucagon stimulates lipolysis

Insulin inhibits fat breakdown and stimulates triglyceride storage

Question 10

3 stages of fatty acid breakdown

Answer 10

1. Activation
   - occurs in cytosol
   - catalyzed by acyl-CoA synthetase
   - produce 2 phosphates
   - Fatty acyl-CoA is a final product
2. Transport of fatty acyl-CoA
3. Beta-Oxidation

Question 11

What is fatty acyl-CoA

Answer 11

Transported from cytosol into mitochondria

Short chain fatty acids are able diffuse directly through the mitochondrial membrane

Long chain fatty acids are transported into the mitochondria with the aid of carnitine

Carnitine – produced from lysine and methionine, or obtained from food

Question 12

What is Beta oxidation

Answer 12

It is the breakdown of fatty acids in the mitochondria to produce NADH, FADH2 and acetyl CoA that can be used to generate energy.

Once fatty acyl-CoA has entered the mitochondria matrix it will undergo β-oxidation.

Question 13

Beta-oxidation process

Answer 13

After activation, fatty acid CoA esters enter the mitochondria for further processing, beta-oxidation

Fatty acids are recycled through the same four steps process

It is a spiral pathway.
Each spiral consists of 4 enzyme-catalysed steps, resulting in release of 1 molecule of acetyl CoA and the fatty acid chain is shortened by 2 carbons - Two carbons are removed each time.

An acetyl CoA is produced with each spiral.
Acetyl CoA then goes on to the citric acid cycle for energy production.

Question 14

Simplified process of fatty acyl CoA in beta-oxidation process

Answer 14

14 carbon Fatty acyl CoA will undergo 6 spirals and get 7 acetyl CoA.

Each spiral will produce fatty acyl CoA shorten by 2C.

C2 will become acetyl CoA itself

Question 15

What are the yields of 1 round of beta oxidation

Answer 15

1 molecule of acetyl CoA
1 molecule of fatty acyl-CoA
1 molecule of FADH2
1 molecule of NADH

Big amount of ATP from acetyl CoA which goes to Kreb cycle and Electron transport chain and NADH and FADH2 which goes to electron transport chain

Hence, fatty acid oxidation yields high amount of energy

Question 16

How to calculate the products of a beta oxidation of a Cn fatty acid?

Answer 16

The oxidation of a Cn fatty acid will produce
n/2 molecules of acetyl CoA
n/2-1 molecules of NADH
n/2-1 FADH2.

Question 17

What is the formula of 1 cycle of beta oxidation?

Answer 17

Cn-acyl-CoA + FAD + NAD+ + H2O + CoA → Cn-2-acyl-CoA + FADH2 + NADH + H+ + acetyl-CoA

Question 18

What is the 4 steps of beta oxidation

Answer 18

Beta-oxidation consists of four steps:

1) Dehydrogenation catalyzed by acyl-CoA dehydrogenase, which removes two hydrogens between carbons 2 and 3.
2) Hydration catalyzed by enoyl-CoA hydratase, which adds water across the double bond.
3) Dehydrogenation catalyzed by 3-hydroxyacyl-CoA dehydrogenase, which generates NADH.
4) Thiolytic cleavage catalyzed beta-ketothiolase, which cleaves the terminal acetyl-CoA group and forms a new acyl-CoA which is two carbons shorter than the previous one.

The shortened acyl-CoA then reenters the beta-oxidation pathway.