Lecture 31: Lipid Catabolism

Question 1

Refresher on Lipids

What are the types of lipids?

Answer 1

Simple (Fat, Oil, Wax)
Complex (Phospholipids, glycolipids)
Sterol (Cholesterol, others)

Question 2

Refresher on Lipids

Which of the lipids are triacylglycerols?

Focus of this section

Answer 2

Fat and oil (fatty acids)

Question 3

Catabolism of Lipids

What are triacylglycerols split into?

Answer 3

Glycerol and fatty acids

Question 4

Lipid Importance

Why are lipids important to cells?

Answer 4

Fuel
* 1/3 of out energy comes from dietary triacylglycerols
* 80% energy needs of mammalian heart and liver are met by oxidation of fatty acids
* many hibernating animals rely on stored fats for energy

Building blocks
* phospholipids
* glycolipids

Precursors of hormones and messengers
Used to target proteins to membrane sites

Question 5

Triacylglycerol as energy storage

What is one advantage of fats over polysaccharides?

Answer 5

They are highly reduced
-carry more energy per carbon

Question 6

Triacylglycerol as energy storage

What is a second advantage of fats over polysaccharides?

Answer 6

Anhydrous
-carry less water since they are nonpolar
-can carry more than 6x the energy per gram than a gram of glycogen

Question 7

Triacylglycerol as energy storage

What type of energy storage are these?

Answer 7

Long term, slow delivery
(vs short term, quick energy of glucose and glycogen)

Question 8

Triacylglycerol as energy storage

Where is the main storage?

Answer 8

adipose tissue

Question 9

Digestion and Transportation

Where do triacylglycerols form Lipid Droplets?

of Fats

Answer 9

stomach

Question 10

Digestion and Transportation

What is secreted by the gall bladder and how does it help digestion?

of fats

Answer 10

Bile acids, as bile salts
renders the droplets more accesible to digestion by lipases

Question 11

Digestion and Transportation

What is a lipase?

Answer 11

Secreted by the pancreas, digests the triacylglycerols into 2 fatty acids and monoacylglycerol

Question 12

Digestion and Transportation

How and where are digestion products carried?

Answer 12

as micelles to the intestinal epithelium cells to be absorbed

Question 13

Digestion and Transportation

What happens to triacylglycerols in the intestine?

Answer 13

reform from free fatty acids and monoacyglycerol
packaged into lipoproteins particles called chylomicrons

Question 14

Digestion and Transportation

Where do the chylomircons take the triacylglycerols?

Answer 14

from the intestine to the blood

Question 15

Breakdown of Triacyglycerols

What are some lipase regulated by?

Answer 15

The hormones glucagon and epinephrine

Question 16

Breakdown of Triacyglycerols

What are the glycerols absorbed by and converted to?

Answer 16

Liver

Glycolytic intermediates (for glycolysis or glyconeogenesis)

Question 17

Breakdown of Triacyglycerols

What are the fatty acids absorbed by and converted to?

Answer 17

transported to other tissues for fuel

Question 18

Glycerol

What activates glycerol and what is it at the expense of?

Answer 18

Glycerol Kinase

ATP

Question 19

Glycerol

Why is it ok that this reaction uses ATP?

Answer 19

Later reactions recover more ATP than what this uses, so it covers the cost

Question 20

Fatty Acid Transport

Where are they transported into for b-oxidation?

Answer 20

The mitochondria, from the cytosol

Question 21

Fatty Acid Transport

Can fatty acids difuse across the mitochondrial membrane freely?

Answer 21

Only if they are under 12 carbons, those over have to be activated into fatty acyl-CoA for transport

Question 22

Fatty Acid Transport

What enam catalyzes the reaction to allow these larger fatty acids across?

Answer 22

Acyl CoA synthetase on the mitochondrial membrane

Question 23

Fatty acid Transport

What actually transports these larger fatty acids?

Answer 23

Carnitine

Question 24

b-Oxidation of Fatty acyl-CoA

What does this generally consist of?

Answer 24

oxidative conversion of 2C units into acetyl CoA (shorted by 2C each round) with concomitant generation of NADH and FADH2

Question 25

# b-Oxidation of Fatty acyl-CoA What does each round of degradation involve?

Answer 25

1. Oxidation of acyl-CoA, catalyzed by *acyl CoA dehydrongenase* to generate **trans-delta2-enoyl CoA and FADH2** 2. Hydration of trans-delta2-enoyl CoA by *enoyl CoA hydratase* to generate **L-3-hydroxyacyl CoA** 3. Oxidation of L-3-hydroxyacyl CoA by *L-3-hydroxyacyl CoA dehydrogenase* to generate **3-ketoacyl CoA and NADH** 4. Cleavage of the 3-ketoacyle CoA by *thiolase* forms **acetyl CoA and a fatty acid chain (acyl CoA) that is 2 carbons shorter** (thiolysis)

Question 26

# Complete Oxidation of Fatty Acids What is stage 1?

Answer 26

Oxidative conversion of 2C units into acetyl-CoA via b-oxidation with concomitant generation of NADH and FADH2

Question 27

# Complete Oxidation of Fatty Acids What is the general reaction of Stage 1?

Answer 27

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

Question 28

# Complete Oxidation of Fatty Acids What is stage 2?

Answer 28

oxidation of acetyl-CoA into CO2 via CAC with concomitant generation of NADH and DAFH2

Question 29

# Complete Oxidation of Fatty Acids What is the general reaction of stage 2?

Answer 29

Acetyl-CoA + 3 NAD + FAD + GDP + Pi + 2 H2O --> 2 CO2 + 3NADH + FADH2 + GTP + CoA +3 H

Question 30

# Complete Oxidation of Fatty Acids How many ATP does acetyl-CoA produce overall?

Answer 30

10 (3 NADH = 7.5 ATP 1 FADH2 = 1.5 ATP 1 GTP = 1 ATP)

Question 31

# Complete Oxidation of Fatty Acids What is stage 3?

Answer 31

generation of ATP from stage 1's NADH and FADH2 via the respiratory chain

Question 32

# Complete Oxidation of Fatty Acids What is stage 3's ATP generation?

Answer 32

FADH2 = 1.5 ATP NADH = 2.5 ATP

Question 33

# Complete Oxidation of Fatty Acids How many ATP does a C16 acyl-CoA with 7 rounds of b-oxidation produce?

Answer 33

8 acetyl-Coa = 10 x 8=80 7 FADH2 = 1.5 x 7 = 10.5 7 NADH = 2.5 x 7 = 17.5 Activation = -2 Total: 106 ATP

Question 34

# Complete Oxidation of Fatty Acids Q from Lecture: How about the b-oxidation of myristyl-CoA (C14:0)? | How many ATP is generated

Answer 34

6 rounds of b-oxidation 70+9+15-2 92 ATP

Question 35

# Oxidation of Unsaturated Fatty Acids What do unsaturated fatty acids contain?

Answer 35

cis double bonds

Question 36

# Oxidation of Unsaturated Fatty Acids What is required to oxidize unsaturated fatty acids?

Answer 36

2 additional enams: * Isomerase (converts the cis double bond to trans at C3) * reductase (reduces cis doubles bonds not at C3)

Question 37

# Oxidation of Unsaturated Fatty Acids Which unsaturated FA require these enams? | isomerase and reductase

Answer 37

Monounsaturated: require isomerase Polyunsaturated: requires both

Question 38

# Oxidation of Unsaturated Fatty Acids Why do unsaturated FA need extra enams?

Answer 38

Because the cis double bonds mean that they are not able to be a substrate from enoyl-CoA hydratase

Question 39

# Oxidation of Odd-numbered FA What forms from oxidation of odd numbered FA?

Answer 39

Propionyl-CoA Carboxylase

Question 40

# Oxidation of Odd-numbered FA What is Propionyl-CoA Carboxylase?

Answer 40

a biotin enzyme, it adds a carbon to propionyl CoA to form methylmalonyl CoA (so that it can go through b-oxidation)

Question 40

# Oxidation of Odd-numbered FA Do odd-numbered FA use b-oxidation?

Answer 40

yes, but b-oxidation cannot process 3C units, so they have to be converted into an even number form

Question 41

# Oxidation of Odd-numbered FA What is formed from Methylmalonyl CoA?

Answer 41

Succinyl CoA (CAC component) using methylmalonyl CoA Mutase which requires vitamin B12

Question 42

# Formation of Ketone Bodies Can fatty acids be used to synthesize glucose?

Answer 42

No, since acetyl-CoA cannot synthesize oxaloacetate

Question 43

# Formation of Ketone Bodies What happens when the level of oxaloacetate decreases? | Due to diabetes or starvation

Answer 43

The CAC slows down and Acetyl-CoA cannot be brought into the CAC. Instead it is converted into ketone bodies

Question 44

# Formation of Ketone Bodies What ketone bodies does Acetyl-CoA form?

Answer 44

Acetoacetate, D-3-hydroxybutyrate, and acetone

Question 45

# Formation of Ketone Bodies What can excess production of ketone bodies lead to?

Answer 45

Acidosis (decreases pH of the blood, can threaten the persons life)