Fatty Acid Catabolism Flashcards
Tissue fuel stores in average 70 kg human
Fatty Acids are amphipathic meaning?
They are hydrophobic (tail = long chain of carbon) and hydrophilic (head= carboxylic acid)
-Polar head = faces cytoplasm
-Tail – in membrane
Fatty acids are saturated or unsaturated meaning?
Saturated = no double bond
Unsaturated = double bond
Fatty acids are saturated or unsaturated meaning?
Saturated = no double bond
Unsaturated = double bond
Describe the abbreviation of fatty acids (eg. what does 18:0 mean?)
first number = number of carbon
Second number = is there a double bonds
Eg. 18:0
18 carbons and no double bond
Describe what this abbreviation means
18 = carbons
1 = double bond on carbon 9
Cis bond
hydrogens on same side of double bonds
Trans bond
hydrogen on opposite side of double bonds
What does this abbreviation mean
-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
What does this abbreviation mean
-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
T or F: Trans fats are good for you
-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
T or F: Trans fats are good for you
-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
Name 2 fatty acids/triacyl glycerides (TAGS)
- Triacylglycerol
- Tristearin (glycerol + 3 stearate molecules)
Which fatty acids are solid and liquid at room temperature?
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
Which fatty acids are solid and liquid at room temperature?
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
What are the 3 primary sources of TAGS
- The diet
- de novo synthesis (liver)
- Storage depots in adipocytes
3 characteristics of storing TAGS
- Unlimited storage capacity
- If storage is unregulated it can lead to obesity
- Release of stored fats is hormonally-regulated (eg. glucagon promotes the release of TAGS)
What 3 enzymes work together to convert TAG -> Free fatty acids + glycerol
- Adipose TriGlyceride Lipase (ATGL)
- Hormone-Sensitive Lipase (HSL)
- MonoacylGlycerol Lipase (MGL)
What are the 3 steps of Fatty acid catabolism (breakdown0
- Activation of FA
- Transport of FA
- β-Oxidation
Step 1 FA activation (catabolism)
- This reaction occurs because it is a coupled reaction, where the hydrolysis of pyrophosphate (2 ATP) makes this reaction favourable
2 characteristics of step 1 FA activation (catabolism0
- Multiple genes code for acyl-CoA synthetase (each acyl-CoA synthetase generates multiple protein isoforms)
- 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)
Step 2 FA transport uses what shuttle system
The carnitine shuttle
Step 1 of FA transport (carnitine shuttle)
Acylation of carnitine is catalyzed by carnitine palmitoyltransferase I (CPT I)
Step 2 of FA Transport (carnitine shuttle)
Fatty acyl-carnitine enter the intermembrane space through porin pores and get access to the mitochondrial matrix by passing through a translocase (protein carrier).
Step 3 of FA Transport (carnitine shuttle)
Deacylation of Fatty acyl-carnitine catalyzed by carnitine palmitoyltransferase II (CPT 2) (reverse of step 1)
Why do we use the carnitine shuttling process?
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
Step 3 β-Oxidation 4 characteristics
- Occurs in the mitochondria matrix
- Modification occurs at the β-carbon
- Chain is shortened by 2 carbons at a time
- Cyclic pathway of 4 reactions
How does Step 3 β-oxidation shorten the carbon chain (2 steps)
- Oxidation of the β-carbon in a series of steps in which two carbons shorten the fatty acyl chain at a time
- This four step process will release a two carbons fragment, acetyl-CoA, at each cycle.
Example: Palmitic acid (16:0)
4 steps of B-Oxidation
Reaction 1 B-oxidation
Dehydrogenation of acyl-CoA in trans-Δ2-Enoyl-CoA catalyzed by Acyl-CoA Dehydrogenases (ACAD)
Explain the 4-step process of Acyl-CoA Dehydrogenase for reaction 1 of B-oxidation
- These enzymes are bound to FAD
- Upon dehydrogenation, FADH2 will be generated.
- 2 Electrons will be transferred to the electron-transferring flavoprotein (ETF) which is also bound to an FAD molecule.
- These electrons will be passed to CoQ via the ETF-Q oxidoreductase.
Exam Question: Can you name the 4 enzymes that transport e- to coenzyme Q
1)complex I
2) complex II
3) Glycerol 3-phosphate
4) FAD
Reaction 2 β-oxidation
Hydration of trans- Δ2-Enoyl-CoA to form L-3-hydroxyacyl-CoA catalyzed by enoyl-CoA hydratase
Reaction 3 β-oxidation
Dehydrogenation of L-3-hydroxyacyl-CoA to form 3-ketoacyl-CoA catalyzed by 3-L-hydroxyacyl-CoA dehydrogenase
-Upon dehydrogenation, NADH will be generated.
Reaction 3 β-oxidation
Dehydrogenation of L-3-hydroxyacyl-CoA to form 3-ketoacyl-CoA catalyzed by 3-L-hydroxyacyl-CoA dehydrogenase
-Upon dehydrogenation, NADH will be generated.
Reaction 4 β-oxidation
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.
In reaction 4 what does our β-carbon become
Carbon 1
What does 1 cycle of β-oxidation produce?
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
How many ATP will be generated by the b-oxidation of a C16:0 fatty acid?
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
What happens if we have b-oxidation of odd number fatty acids?
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.
How many ATP will be generated by the b-oxidation of a C15:0 fatty acid?
How many ATP will be generated by the b-oxidation of one molecule of palmitoleic acid?
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
How many ATP will be generated by the b-oxidation of one molecule of linoleic acid?
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)
If the double bond is located at odd carbon number
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
