Lecture 31: Lipid Catabolism Flashcards

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1
Q

Refresher on Lipids

What are the types of lipids?

A

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

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2
Q

Refresher on Lipids

Which of the lipids are triacylglycerols?

Focus of this section

A

Fat and oil (fatty acids)

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3
Q

Catabolism of Lipids

What are triacylglycerols split into?

A

Glycerol and fatty acids

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4
Q

Lipid Importance

Why are lipids important to cells?

A

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

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5
Q

Triacylglycerol as energy storage

What is one advantage of fats over polysaccharides?

A

They are highly reduced
-carry more energy per carbon

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6
Q

Triacylglycerol as energy storage

What is a second advantage of fats over polysaccharides?

A

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

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7
Q

Triacylglycerol as energy storage

What type of energy storage are these?

A

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

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8
Q

Triacylglycerol as energy storage

Where is the main storage?

A

adipose tissue

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9
Q

Digestion and Transportation

Where do triacylglycerols form Lipid Droplets?

of Fats

A

stomach

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10
Q

Digestion and Transportation

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

of fats

A

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

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11
Q

Digestion and Transportation

What is a lipase?

A

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

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12
Q

Digestion and Transportation

How and where are digestion products carried?

A

as micelles to the intestinal epithelium cells to be absorbed

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13
Q

Digestion and Transportation

What happens to triacylglycerols in the intestine?

A

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

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14
Q

Digestion and Transportation

Where do the chylomircons take the triacylglycerols?

A

from the intestine to the blood

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15
Q

Breakdown of Triacyglycerols

What are some lipase regulated by?

A

The hormones glucagon and epinephrine

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16
Q

Breakdown of Triacyglycerols

What are the glycerols absorbed by and converted to?

A

Liver

Glycolytic intermediates (for glycolysis or glyconeogenesis)

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17
Q

Breakdown of Triacyglycerols

What are the fatty acids absorbed by and converted to?

A

transported to other tissues for fuel

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18
Q

Glycerol

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

A

Glycerol Kinase

ATP

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19
Q

Glycerol

Why is it ok that this reaction uses ATP?

A

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

20
Q

Fatty Acid Transport

Where are they transported into for b-oxidation?

A

The mitochondria, from the cytosol

21
Q

Fatty Acid Transport

Can fatty acids difuse across the mitochondrial membrane freely?

A

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

22
Q

Fatty Acid Transport

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

A

Acyl CoA synthetase on the mitochondrial membrane

23
Q

Fatty acid Transport

What actually transports these larger fatty acids?

A

Carnitine

24
Q

b-Oxidation of Fatty acyl-CoA

What does this generally consist of?

A

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

25
Q

b-Oxidation of Fatty acyl-CoA

What does each round of degradation involve?

A
  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)
26
Q

Complete Oxidation of Fatty Acids

What is stage 1?

A

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

27
Q

Complete Oxidation of Fatty Acids

What is the general reaction of Stage 1?

A

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

28
Q

Complete Oxidation of Fatty Acids

What is stage 2?

A

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

29
Q

Complete Oxidation of Fatty Acids

What is the general reaction of stage 2?

A

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

30
Q

Complete Oxidation of Fatty Acids

How many ATP does acetyl-CoA produce overall?

A

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

31
Q

Complete Oxidation of Fatty Acids

What is stage 3?

A

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

32
Q

Complete Oxidation of Fatty Acids

What is stage 3’s ATP generation?

A

FADH2 = 1.5 ATP
NADH = 2.5 ATP

33
Q

Complete Oxidation of Fatty Acids

How many ATP does a C16 acyl-CoA with 7 rounds of b-oxidation produce?

A

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

34
Q

Complete Oxidation of Fatty Acids

Q from Lecture: How about the b-oxidation of myristyl-CoA (C14:0)?

How many ATP is generated

A

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

35
Q

Oxidation of Unsaturated Fatty Acids

What do unsaturated fatty acids contain?

A

cis double bonds

36
Q

Oxidation of Unsaturated Fatty Acids

What is required to oxidize unsaturated fatty acids?

A

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

37
Q

Oxidation of Unsaturated Fatty Acids

Which unsaturated FA require these enams?

isomerase and reductase

A

Monounsaturated: require isomerase
Polyunsaturated: requires both

38
Q

Oxidation of Unsaturated Fatty Acids

Why do unsaturated FA need extra enams?

A

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

39
Q

Oxidation of Odd-numbered FA

What forms from oxidation of odd numbered FA?

A

Propionyl-CoA Carboxylase

40
Q

Oxidation of Odd-numbered FA

What is Propionyl-CoA Carboxylase?

A

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

40
Q

Oxidation of Odd-numbered FA

Do odd-numbered FA use b-oxidation?

A

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

41
Q

Oxidation of Odd-numbered FA

What is formed from Methylmalonyl CoA?

A

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

42
Q

Formation of Ketone Bodies

Can fatty acids be used to synthesize glucose?

A

No, since acetyl-CoA cannot synthesize oxaloacetate

43
Q

Formation of Ketone Bodies

What happens when the level of oxaloacetate decreases?

Due to diabetes or starvation

A

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

44
Q

Formation of Ketone Bodies

What ketone bodies does Acetyl-CoA form?

A

Acetoacetate, D-3-hydroxybutyrate, and acetone

45
Q

Formation of Ketone Bodies

What can excess production of ketone bodies lead to?

A

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