Download - New 5 Fatty Acid Catabolism
-
8/13/2019 New 5 Fatty Acid Catabolism
1/25
Fatty Acid Catabolism
A AngelesChem 40
-
8/13/2019 New 5 Fatty Acid Catabolism
2/25
Digestion, Mobilization and Transport of FatsRefer to ourpreviousdiscussion
-
8/13/2019 New 5 Fatty Acid Catabolism
3/25
About one third of our energy needs comes from
dietary triacylglycerols ~80% of energy needs of mammalian heart and liverare met by oxidation of FA
Fatty Acid Catabolism
(chemically inert) and slow delivery
Fats are hydrolyzed into fatty acids and glycerol inthe cytoplasm
Energy derived from glycerol ~5%
-
8/13/2019 New 5 Fatty Acid Catabolism
4/25
-
8/13/2019 New 5 Fatty Acid Catabolism
5/25
Glycerol can enter the glycolytic pathway
What happens to glycerol?
How many ATPs can we derive from1 mol of glycerol?
-
8/13/2019 New 5 Fatty Acid Catabolism
6/25
Fat (fatty acid) catabolism provides:
1. Reducing equivalents that will ultimately produceATP2. Acetyl-CoA that can
Fatty Acid Catabolism
be converted to ketone bodies (alternate fuel
source for brain and other tissues) in the liver be used for cholesterol biosynthesis act as a biosynthetic precursor
-
8/13/2019 New 5 Fatty Acid Catabolism
7/25
-oxidation of fatty acids occurs in mitochondria Small (< 12 C) fatty acids diffuse freely across
mitochondrial membranes Larger fatty acids are transported via acyl-
Fatty Acid Transport to the Mitochondria
carn t ne carn t ne transporter
-
8/13/2019 New 5 Fatty Acid Catabolism
8/25
Fatty Acid Transport to the Mitochondria1. Fatty acid activation in the cytosol
Fatty acid + CoA + ATP Fatty acyl-CoA + AMP + 2Pi
Favorable! G o=-34 kJ/mol
-
8/13/2019 New 5 Fatty Acid Catabolism
9/25
2. Fatty acid transferto carnitine to formfatty-acyl carnitine
Fatty AcidTransport to the
Mitochondria
This FAsfate is
sealed.
3. Transport(facilitateddiffusion)
4. Removal of carnitinein the matrix
-
8/13/2019 New 5 Fatty Acid Catabolism
10/25
Fatty Acid Transport to the Mitochondria
-
8/13/2019 New 5 Fatty Acid Catabolism
11/25
Occurs in three stages consider the oxidation of
Oxidation of Fatty Acids
palmitate
-
8/13/2019 New 5 Fatty Acid Catabolism
12/25
STEP 1:
Dehydrogenation ofFatty Acyl CoA
Formation of double
-oxidation of Fatty Acids
bond between
carbons (oxidation) Yields 1 FADH 2
-
8/13/2019 New 5 Fatty Acid Catabolism
13/25
STEP 2:
Hydration of doublebond
-OH is added to the
-oxidation of Fatty Acids
carbon
-
8/13/2019 New 5 Fatty Acid Catabolism
14/25
STEP 3:
Dehydrogenation at carbon
-OH carbonyl carbon
-oxidation of Fatty Acids
(oxidation) Yields 1 NADH Priming for nucleophilic
attack
-
8/13/2019 New 5 Fatty Acid Catabolism
15/25
STEP 4:
Thiolysis Yields 1 acetyl CoA + acyl
CoA (n-2)
-oxidation of Fatty Acids
-
8/13/2019 New 5 Fatty Acid Catabolism
16/25
Summary:
Every other carbon is converted to aC=O
Allows nucleophilic attack by CoA-SH
-oxidation of Fatty Acids
on remaining chain 1 CoA-SH is used for every 2 carbon
segment to release acetyl-CoA
Each round produces: 1 FADH2, 1NADH, 1 Acetyl-CoA (2 in the lastround)
-
8/13/2019 New 5 Fatty Acid Catabolism
17/25
How many rounds of -
oxidation occurs for a FAwith even numberedcarbons?
-oxidation of Fatty Acids
(n/2)-1 rounds
-
8/13/2019 New 5 Fatty Acid Catabolism
18/25
How many ATPs are formed in one complete
oxidation of stearic acid? Activation: -2 ATPs (the FA already has CoA, no
need to subtract)
-oxidation of Fatty Acids
8 rounds of -oxidation: 8(1 FADH 2 and 2 NADH) 9 Acetyl CoAs go into the TCA Answer: 120 ATPs Compare this energy yield with that of one
glucose molecule
-
8/13/2019 New 5 Fatty Acid Catabolism
19/25
-oxidation of Fatty Acids
What happens if the FA is unsaturated?
Bypasses the initialdehydrogenation step Cis-isomer Trans-isomer
2 Subtract 1.5 ATPs per
unsaturation
-
8/13/2019 New 5 Fatty Acid Catabolism
20/25
Most dietary fatty acids are even-numbered
Many plants and some marine organisms alsosynthesize odd-numbered fatty acids
-oxidation of Fatty Acids
- - -numbered fatty acids
Bacterial metabolism in the rumen of ruminants
also produces propionyl-CoA
-
8/13/2019 New 5 Fatty Acid Catabolism
21/25
Subtract 6 ATPs in the last
TCA cycle
-oxidation of Fatty
Acids
-
8/13/2019 New 5 Fatty Acid Catabolism
22/25
How many ATPs are formed in one complete
oxidation of pentadecanoic acid? Activation: -2 ATPs -
-oxidation of Fatty Acids
6 Acetyl CoAs go into the TCA 1 succinyl CoA goes into the TCA
Answer: 86 ATPs
-
8/13/2019 New 5 Fatty Acid Catabolism
23/25
Can we live off fatty acids alone?
Entry of acetyl-CoA into citric acid cycle requiresoxaloacetate When oxaloacetate is depleted, acetyl-CoA is converted
Ketone Body Production
Production of ketone bodies increases duringstarvation
Ketone bodies are released by liver to bloodstream Organs other than liver can use ketone bodies as fuels
-
8/13/2019 New 5 Fatty Acid Catabolism
24/25
Acetone can be exhaled
Acetoacetate and -hydroxybutyrate are transported inthe blood to other tissues
Ketone Body
Production
Too high levels of acetoacetate
and -hydroxybutyrate lower bloodpH dangerously (acidosis)
Accumulation of ketone bodies inthe bloodstream ketosis
-
8/13/2019 New 5 Fatty Acid Catabolism
25/25
Synthesis
Fats are an important energy source in animals Two-carbon units in fatty acids are oxidized in a four-step -
oxidation process into acetyl-CoA
Fatty Acid Catabolism
In the process, NADH and FADH 2 are formed willeventually be used in the ETC to produce ATP
Acetyl-CoA formed in the liver can be either oxidized via thecitric acid cycle or converted to ketone bodies that serve asfuels for other tissues