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2) Biochemistry II > Fatty Acid Catabolism > Flashcards

Fatty Acid Catabolism Flashcards

1
Q

How do lipids yield energy?

A

Through B-oxidation of fatty acids

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2
Q

The liver and heart derive __% of energy from fatty acid oxidation.

A

80%

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3
Q

What is B-oxidation in short?

A

A four-step enzyme catalyzed process of oxidative removal of 2-carbon units from FA to form acetyl-CoA

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4
Q

Why are TG the best storage fuels?

A
  • FA chains are highly reduced compounds (yield more energy)
  • Insoluble in water, do not increase osmolarity in the blood
  • Relatively inert; no risk of undesirable reactions when they are stored in the cell
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5
Q

What is the main form of storage in adipose tissue?

A

Storage of fat in the form of TG

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6
Q

Why don’t TG increase osmolarity in the blood?

A

Because they are hydrophobic

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7
Q

How are fats absorbed?

A

1) Bile salts emulsify fat in the small intestine
2) Intestinal lipases degrade TG into diacylglycerol, monoacylglycer, FFA, and glycerol
3) Intestinal cells absorb FA and they re-esterify them into TG
4) TG are incorporated into chylomicrons
5) Chylomicrons transport TG to tissues
6) Endothelial cells cleave the FA out of the TG from the chylomicrons with lipoprotein lipases
7) FA are absorbed into the cell

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8
Q

Name the lipoproteins in terms of lowest density to highest density.

A
  • Chylomicrons (lowest)
  • VLDL
  • ILDL
  • LDL
  • HDL (highest)
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9
Q

What are the lipoprotein lipases of endothelial cells activated by? What do they do?

A
  • By apo-C-II

- Cleave the FA out of the TG from the chylomicrons

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10
Q

How can FA be used in the cell?

A
  • To generate energy

- Storage in adipose cells by being re-esterified to TG

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11
Q

Adipocytes contain a lot of fatty acids in the form of _______.

A

lipid droplets

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12
Q

How do adipocytes release FA? Which receptor is implicated?

A

When the glucagon receptor binds to glucagon (GPCR)

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13
Q

What does the binding of glucagon to its receptor lead to?

A

Activation of PKA

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14
Q

What does activated PKA do?

A

Phosphorylates perilipin (proteins) on the lipid droplet

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15
Q

What are the two consequences of phosphorylated perilipin?

A
  • CGI58 (comparitive gene identification) gets dissociated and activates adipose TG lipase (ATGL)
  • PKA phosphorylates hormone-sensitive lipase (HSL)
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16
Q

What does ATGL do?

A

Converst TG into diacylglycerol and a free fatty acid

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17
Q

What does HSL do?

A

Only attacks diacylglycerol, converting it into a free fatty acid and monoacylglycerol

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18
Q

What does monoacylglycerol lipase do?

A

Attacks only on the monoacylglycerol and separates them into a free fatty acid and a glycerol

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19
Q

What happens when free fatty acids are broken off?

A
  • Are in the cytoplasm

- Eventually let loose in the circulation

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20
Q

How are free fatty acids transported in circulation?

A

They are always bound to serum albumin

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21
Q

How many fatty acids can serum albumin bind? What are they called?

A
  • Up to 10 NEFAs

- Non-esterified fatty acids

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22
Q

What do fatty acids go through to release energy?

A

B-oxidation, TCA cycle, and the respiratory chain

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23
Q

What is the fate of glycerol during TG catabolism?

A
  • Phosphorylated by glycerol kinase to form glycerol-3-phosphate
  • Oxidized by glycerol-3-phosphate dehydrogenase to form dihydroxyacetone phosphate
  • Isomerized by triose phosphate isomerase to form glyceraldehyde-3-phosphate
  • Can enter the glycolytic pathway
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24
Q

What % of the energy in a TG does glycerol provide?

A

5%

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25
Q

What enzyme activates a FA so that it can undergo B-oxidation?

A

Fatty-acyl-CoA synthetase

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26
Q

How does fatty-acyl-CoA synthetase work?

A

1) Adenylation by ATP
2) Coenzyme A attacks
3) Forms fatty acyl-CoA and a pyrophosphate (degraded)

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27
Q

What is the activated fatty acid?

A

Fatty-acyl-CoA

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28
Q

Where are the enzymes of B-oxidation held?

A

Stuck within the mitochondria

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29
Q

What can fatty-acyl-CoA be used for?

A

To synthesize longer membrane lipids (FA synthesis)

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30
Q

Can fatty acids diffuse across mitochondrial membranes?

A
  • Under 12 carbons, FA diffuse freely across the mitochondrial membranes
  • Longer fatty acids need the help of a transporter (facilitated diffusion)
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31
Q

How do longer fatty acids cross the mitochondrial membrane?

A
  • Facilitated diffusion

- Need the help of a transporter

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32
Q

How do transporters help longer fatty acids cross the mitochondrial membrane?

A
  • Outer membrane:
  • -> Carnitine acyltransferase 1 (removes coenzyme A and replaces it with Carnitine on the FA)
  • -> Acyl carnitine transporter can now transport the FA that contains carnitine
  • Inner membrane
  • -> Carnitine acyltransferase II (replaces the carnitine with Coenzyme A on the fatty acid)
33
Q

Is the fatty acid activated inside the matrix of the mitochondria? How?

A
  • Yes

- Due to carnitine acyltransferase II

34
Q

How many steps is B-oxidation?

A

4-step enzyme catalyzed

35
Q

At which end does B-oxidation occur?

A

At the carboxyl end

36
Q

What does B-oxidation release? Where does it go?

A
  • Releases Acetyl-CoA

- Which can go into the TCA cycle

37
Q

Where does the TCA cycle receive Acetyl-CoA from?

A
  • Beta Acetyl-CoA from B-oxidation

- Acetyl-CoA from glycolysis

38
Q

Where does the NADH and FADH2 produced in the TCA cycle enter?

A

Enters the respiratory chain

39
Q

What are the four enzymes of B-oxidation?

A

1) Acyl-CoA dehydrogenase
2) Enoyl-CoA hydratase
3) B-hydroxyacyl-CoA dehydrogenase
4) Acyl-CoA acetyltransferase (thiolase)

40
Q

What does FAD attack in B-oxidation? What does it do? Which enzyme catalyzes this reaction?

A
  • Attacks the beta carbon
  • Introduces a double bond between alpha and beta carbon
  • Catalyzed by acyl-CoA dehydrogenase
41
Q

Where are the alpha carbons and beta carbons situated on a fatty acid?

A
  • Alpha: 2nd from carboxyl end

- Beta: 3rd from carboxyl end

42
Q

What does enoyl-CoA hydratase do in B-oxidation?

A
  • Adds H2O

- Making the double bond into a single bond

43
Q

What does B-hydroxyacyl-CoA dehydrogenase do in B-oxidation?

A
  • Uses NAD+
  • Removes 2 hydrogens
  • Creates a double bond on the beta carbon towards the O
44
Q

What does the thiolase do in B-oxidation?

A

Adds CoA-SH to the first carbon that leaves a 2-carbon molecule, which is Acetyl-CoA

45
Q

What does the B-oxidation of a C16 fatty acid yield? How many reactions does it take?

A
  • 8 Acetyl-CoA
  • 7 FADH2
  • 7 NADH
  • 7 H+
  • 28 ATP
  • Uses 7 reactions
46
Q

How many ATPs are generated by FADH2? What about NADH?

A
  • FADH2: 1.5 ATP

- NADH: 2.5 ATP

47
Q

What happens in the B-oxidation of an monounsaturated fatty acid?

A
  • Enoyl-CoA isomerase catalyzes the double bond from cis to trans
  • B-oxidation likes trans; can continue
48
Q

What happens in the B-oxidation of a polyunsaturated fatty acid?

A

1) Enoyl-CoA converts the first double bond to trans
2) At the next double bond, dienoyl-CoA reductase converts the two double bond into one (at the position of the first double bond)
3) Enoyl-CoA isomerase will convert the 3,4 trans double bond to 2,3 trans double bond

49
Q

Can B-oxidation occur at 3,4?

A
  • NO, B-oxidation can only occur at the 2,3 position

- Enoyl-CoA isomerase must convert

50
Q

What happens in the B-oxidation of odd numbered fatty acids?

A
  • 2 carbons are removed until it reaches a stage where 3 carbons are left
51
Q

What is the 3-carbon compound left in the B-oxidation of odd numbered fatty called?

A

Propionyl-CoA

52
Q

What happens to propionyl-CoA?

A
  • Vitamin B12 acts as a cofactor
  • Converts it to succinyl-CoA along with other enzymes
  • Succinyl-CoA is in the TCA cycle
53
Q

What is glyoxysome?

A

Peroxisome found in germinating seeds

54
Q

Where are B-oxidation enzymes present?

A
  • Mitochondria

- Peroxisome/Glyoxysome (uncommon)

55
Q

What are the differences in B-oxidation in peroxisomes?

A

○ The FADH2 that is formed in peroxisome is immediately reacted with O2 to form water
○ The NADH that is created is transported back to the cytoplasm or mitochondria for further usage
○ The final product of Acetyl-CoA is thrown out into either the mitochondria or the cytoplasm (since Acetyl-CoA can be metabolized in the cytoplasm)

56
Q

In the B-oxidation of peroxisomes, what is the FADH2 formed reacted with?

A

Immediately reacted with O2 to form water

57
Q

In the B-oxidation of peroxisomes, where is the NADH created transported back to?

A

Back to the cytoplasm or mitochondria for further usage

58
Q

In the B-oxidation of peroxisomes, where is Acetyl-CoA taken to?

A

Either the mitochondria or cytoplasm (Acetyl-CoA can be metabolized in the cytoplasm)

59
Q

The 4 enzymes of B-oxidation have many isoforms. Where are the isoforms specific for long-chain fatty acids found?

A

Bound to the inner membrane of the mitochondria

60
Q

Where are the isoforms specific for short-chain fatty acids found?

A

Floating in the matrix of the mitochondria

61
Q

Which enzymes of B-oxidation are independent proteins?

A

1st and 4th enzyme

62
Q

Where is the fatty-acyl-CoA synthesized in the cytoplasm directed to?

A
  • B-oxidation

- TG synthesis

63
Q

What is the point of commitment for B-oxidation?

A

Carnitine shuttle

64
Q

What inhibits Carnitine acetyltransferase?

A
  • Malonyl-CoA (first intermediate of FA synthesis)
65
Q

What leads to the activation of the Carnitine shuttle?

A

1) Low ATP
2) Stimulates AMPK
3) Inhibits Acetyl-CoA carboxylase
4) Leads to the activation of carnitine shuttle

66
Q

What inhibits Acyl-CoA dehydrogenase? Why?

A
  • High NADH/NAD+ ratio

- When there is more NADH, the catabolic processes are sufficient

67
Q

What kind of fatty acids can undergo Omega-Oxidation?

A
  • Fatty acids with 10 or 12 carbons

- Contain carboxylic groups at both ends

68
Q

Why does Omega-Oxidation yield Acetyl-CoA in a faster manner?

A

Because BOTH ends can undergo B-oxidation

69
Q

Where does Omega-Oxidation occur? In which type of organelle?

A
  • Liver and kidney
  • Endoplasmic reticulum
  • Not a common type
70
Q

What are the three ketone bodies?

A

1) Acetone
2) Acetoacetate
3) D-B-Hydroxybutyrate

71
Q

Where does ketogenesis occur?

A

In the mitochondria of liver cells

72
Q

Where are the three ketone bodies transported to?

A
  • Acetone is exhaled (ketosis fruity breath)

- Acetoacetate and BHB are transported to other tissues

73
Q

Are ketone bodies fat or water soluble?

A

Water-soluble

74
Q

When does ketogenesis occur?

A

During starvation or diabetes

75
Q

Which enzyme of ketogenesis is only present in the mitochondria?

A

HMG-CoA lyase

76
Q

Which enzyme of ketogenesis is also present in the cytoplasm?

A

HMG-CoA synthase

77
Q

What are ketone bodies catalyzed to? When?

A
  • To Acetyl-CoA

- After they reach the tissues to yield energy

78
Q

Which enzyme of the catabolism of ketone bodies is present in all tissues apart from the liver? Why?

A
  • B-ketoacyl-CoA transferase

- Ketone bodies cannot be catalyzed in the liver, must be sent out to other tissues

79
Q

How many Acetyl-CoA, ATP, and H2O molecules are generated from B-Oxidation of a myristic acid (14-C compound)?

A 
6 reactions
7 Acetyl-CoA
6FADH2
6 NADH
24 ATP
6 H2O

2) Biochemistry II (23 decks)

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