Fatty Acid Catabolism Flashcards

1
Q

Tissue fuel stores in average 70 kg human

A
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2
Q

Fatty Acids are amphipathic meaning?

A

They are hydrophobic (tail = long chain of carbon) and hydrophilic (head= carboxylic acid)
-Polar head = faces cytoplasm
-Tail – in membrane

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3
Q

Fatty acids are saturated or unsaturated meaning?

A

Saturated = no double bond
Unsaturated = double bond

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3
Q

Fatty acids are saturated or unsaturated meaning?

A

Saturated = no double bond
Unsaturated = double bond

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4
Q

Describe the abbreviation of fatty acids (eg. what does 18:0 mean?)

A

first number = number of carbon
Second number = is there a double bonds

Eg. 18:0
18 carbons and no double bond

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5
Q

Describe what this abbreviation means

A

18 = carbons
1 = double bond on carbon 9

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6
Q

Cis bond

A

hydrogens on same side of double bonds

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7
Q

Trans bond

A

hydrogen on opposite side of double bonds

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8
Q

What does this abbreviation mean

A

-18 carbons
-3 double bonds at carbon 9, 12, and 15

HINT: When counting carbons always count carbon 1 as the carboxylic acid group and then go down from there

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9
Q

What does this abbreviation mean

A

-18 carbons
-3 double bonds at carbon 9, 12, and 15

HINT: When counting carbons always count carbon 1 as the carboxylic acid group and then go down from there

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10
Q

T or F: Trans fats are good for you

A

-Trans fat are bad for you because they are made commercially (cheap) and have a longer shelf life = increasing bad cholesterol
-Trans fat is mainly found in processed foods

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11
Q

T or F: Trans fats are good for you

A

-Trans fat are bad for you because they are made commercially (cheap) and have a longer shelf life = increasing bad cholesterol
-Trans fat is mainly found in processed foods

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12
Q

Name 2 fatty acids/triacyl glycerides (TAGS)

A
  1. Triacylglycerol
  2. Tristearin (glycerol + 3 stearate molecules)
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13
Q

Which fatty acids are solid and liquid at room temperature?

A

Saturated fats are solid at room temp because they have a higher melting point
Unsaturated fats are liquid at room temp because they have lower melting points

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13
Q

Which fatty acids are solid and liquid at room temperature?

A

Saturated fats are solid at room temp because they have a higher melting point
Unsaturated fats are liquid at room temp because they have lower melting points

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14
Q

What are the 3 primary sources of TAGS

A
  1. The diet
  2. de novo synthesis (liver)
  3. Storage depots in adipocytes
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15
Q

3 characteristics of storing TAGS

A
  1. Unlimited storage capacity
  2. If storage is unregulated it can lead to obesity
  3. Release of stored fats is hormonally-regulated (eg. glucagon promotes the release of TAGS)
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16
Q

What 3 enzymes work together to convert TAG -> Free fatty acids + glycerol

A
  1. Adipose TriGlyceride Lipase (ATGL)
  2. Hormone-Sensitive Lipase (HSL)
  3. MonoacylGlycerol Lipase (MGL)
17
Q

What are the 3 steps of Fatty acid catabolism (breakdown0

A
  1. Activation of FA
  2. Transport of FA
  3. β-Oxidation
18
Q

Step 1 FA activation (catabolism)

A
  • This reaction occurs because it is a coupled reaction, where the hydrolysis of pyrophosphate (2 ATP) makes this reaction favourable
19
Q

2 characteristics of step 1 FA activation (catabolism0

A
  1. Multiple genes code for acyl-CoA synthetase (each acyl-CoA synthetase generates multiple protein isoforms)
  2. Dependent on chain length
    -Short/medium FA (0-10 C) are activated in the mitochondrial matrix and can cross membrane on its own because they have their own acyl-CoA synthetase)
    -Long FA (10-21 C) are activated by acyl-CoA synthetase that are bound on the outer membrane of the mitochondria (need to be converted by acyl-CoAs in the outer mitochondrial membrane before being transported into the mitochondrial matrix)
20
Q

Step 2 FA transport uses what shuttle system

A

The carnitine shuttle

21
Q

Step 1 of FA transport (carnitine shuttle)

A

Acylation of carnitine is catalyzed by carnitine palmitoyltransferase I (CPT I)

22
Q

Step 2 of FA Transport (carnitine shuttle)

A

Fatty acyl-carnitine enter the intermembrane space through porin pores and get access to the mitochondrial matrix by passing through a translocase (protein carrier).

23
Q

Step 3 of FA Transport (carnitine shuttle)

A

Deacylation of Fatty acyl-carnitine catalyzed by carnitine palmitoyltransferase II (CPT 2) (reverse of step 1)

24
Q

Why do we use the carnitine shuttling process?

A

CPT1 is strongly inhibited by malonyl-CoA (regulation):
1) Malonyl-CoA is the first committed intermediate of fatty acid synthesis.
2) Conditions favoring fatty acid synthesis prevent fatty acids from entering the mitochondria where β-oxidation will occurs (catabolism)

Summary: If trying to synthesize FA, we don’t want to break them down so malonyl-CoA inhibits CPT1 so synthesis occurs and not catalysis

25
Q

Step 3 β-Oxidation 4 characteristics

A
  1. Occurs in the mitochondria matrix
  2. Modification occurs at the β-carbon
  3. Chain is shortened by 2 carbons at a time
  4. Cyclic pathway of 4 reactions
26
Q

How does Step 3 β-oxidation shorten the carbon chain (2 steps)

A
  1. Oxidation of the β-carbon in a series of steps in which two carbons shorten the fatty acyl chain at a time
  2. This four step process will release a two carbons fragment, acetyl-CoA, at each cycle.
    Example: Palmitic acid (16:0)
27
Q

4 steps of B-Oxidation

A
28
Q

Reaction 1 B-oxidation

A

Dehydrogenation of acyl-CoA in trans-Δ2-Enoyl-CoA catalyzed by Acyl-CoA Dehydrogenases (ACAD)

29
Q

Explain the 4-step process of Acyl-CoA Dehydrogenase for reaction 1 of B-oxidation

A
  1. These enzymes are bound to FAD
  2. Upon dehydrogenation, FADH2 will be generated.
  3. 2 Electrons will be transferred to the electron-transferring flavoprotein (ETF) which is also bound to an FAD molecule.
  4. These electrons will be passed to CoQ via the ETF-Q oxidoreductase.
30
Q

Exam Question: Can you name the 4 enzymes that transport e- to coenzyme Q

A

1)complex I
2) complex II
3) Glycerol 3-phosphate
4) FAD

31
Q

Reaction 2 β-oxidation

A

Hydration of trans- Δ2-Enoyl-CoA to form L-3-hydroxyacyl-CoA catalyzed by enoyl-CoA hydratase

32
Q

Reaction 3 β-oxidation

A

Dehydrogenation of L-3-hydroxyacyl-CoA to form 3-ketoacyl-CoA catalyzed by 3-L-hydroxyacyl-CoA dehydrogenase
-Upon dehydrogenation, NADH will be generated.

33
Q

Reaction 3 β-oxidation

A

Dehydrogenation of L-3-hydroxyacyl-CoA to form 3-ketoacyl-CoA catalyzed by 3-L-hydroxyacyl-CoA dehydrogenase
-Upon dehydrogenation, NADH will be generated.

34
Q

Reaction 4 β-oxidation

A

Thiolytic cleavage of 3-ketoacyl-CoA to form a Cn-2 acyl-CoA and acetyl-CoA catalyzed by thiolase

-A new CoA is added to the end of Cn-2 acyl chain.

35
Q

In reaction 4 what does our β-carbon become

A

Carbon 1

36
Q

What does 1 cycle of β-oxidation produce?

A

1 cycle of β-oxidation produces:
1 FADH2
1 NADH + H+
1 acetyl-CoA

1 acetyl-CoA (TCA cycle) produces:
3 NADH
1 FADH2
1 GTP (ATP)

** 1 FADH2 = 1.5 ATP
** 1 NADH + H+ = 2.5 ATP

37
Q

How many ATP will be generated by the b-oxidation of a C16:0 fatty acid?

A

1) Need 7 rounds of B-oxidation (because the last cycle produces 2 acetyl-coa)
-8 acetyl-CoA will be produced (C16/2)
2) 7FADH2, 7 NADH, and 8 acetyl-CoA are produced
(1.5ATP x 7 + 2.5ATP x 7 + ((24x2.5) + (8 x 1.5) + (1 x 8 atp)) = 108 ATP (B-oxidation)- 2ATP investment (FA activation) = 106 ATP

38
Q

What happens if we have b-oxidation of odd number fatty acids?

A

The last oxidation cycle produces a 3 carbons molecule called propionyl-CoA which is converted to Succinyl-CoA (TCA cycle intermediate). Therefore, propionyl-CoA (succinyl-CoA) will generate:
1) 1 GTP (Need 1 ATP to convert propionyl coa to succinyl coa so production of 1 gtp gets cancelled out)
2) 1 FADH2
3) 1 NADH
4) an extra TCA cycle intermediate.

39
Q

How many ATP will be generated by the b-oxidation of a C15:0 fatty acid?

A
40
Q

How many ATP will be generated by the b-oxidation of one molecule of palmitoleic acid?

A

Things to remember:
If the double bond is located at odd carbon number eg. D9, D11 or D13:
1) Use of Enoyl-CoA isomerase
2) Skip reaction 1 of b-oxidation cycle so minus 1 FADH2 in in net yield

41
Q

How many ATP will be generated by the b-oxidation of one molecule of linoleic acid?

A

Things to remember:
IF the double bond is located at odd carbon number eg. D9, D11 or D13:
1. Use of Enoyl-CoA isomerase
2. Skip reaction 1 of b-oxidation cycle so minus 1 FADH2 in in net yield

IF the double bond is located at even carbon number eg. D8, D12 or D14:
1. Use of 2,4 Dienoyl-CoA reductase and Enoyl-CoA isomerase
2. Oxidation of one molecule of NADPH (equivalent to 2.5 ATP) go through all four steps of b-oxidation cycle (plus the two extra steps to resolve the double bond in C4)

42
Q

If the double bond is located at odd carbon number

A

eg. Δ9, Δ11 or Δ13
1) Use of Enoyl-CoA isomerase
2) Skip reaction 1 of β-oxidation cycle so minus 1 FADH2 in in net yield